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Sample records for braun lipoprotein mutant

  1. Global gene expression of a murein (Braun) lipoprotein mutant of Salmonella enterica serovar Typhimurium by microarray analysis.

    Science.gov (United States)

    Fadl, A A; Galindo, C L; Sha, J; Klimpel, G R; Popov, V L; Chopra, A K

    2006-06-01

    Braun/murein lipoprotein (Lpp) is one of the major outer membrane components of gram-negative enteric bacteria involved in inflammatory responses and septic shock. In previous studies, we reported that two copies of the lipoprotein (lpp) gene (designated as lppA and lppB) existed on the chromosome of Salmonella enterica serovar Typhimurium. Deletion of both lppA and lppB genes rendered Salmonella defective in invasion, motility, induction of cytotoxicity, and production of inflammatory cytokines/chemokines. The lppAB double-knockout (DKO) mutant was attenuated in mice, and animals immunized with this mutant were protected against subsequent challenge with lethal doses of wild-type (wt) S. Typhimurium. To better understand how deletion of the lpp gene might affect Salmonella virulence, we performed global transcriptional profiling of the genes in the wt and the lppAB DKO mutant of S. Typhimurium using microarrays. Our data revealed alterations in the expression of flagellar genes, invasion-associated type III secretion system genes, and transcriptional virulence gene regulators in the lppAB DKO mutant compared to wt S. Typhimurium. These data correlated with the lppAB DKO mutant phenotype and provided possible mechanism(s) of Lpp-associated attenuation in S. Typhimurium. Although these studies were performed in in vitro grown bacteria, our future research will be targeted at global transcriptional profiling of the genes in in vivo grown wt S. Typhimurium and its Lpp mutant.

  2. Comparative Global Gene Expression Profiles of Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant at Flea and Human Body Temperatures

    Directory of Open Access Journals (Sweden)

    Cristi L. Galindo

    2010-01-01

    Full Text Available Braun/murein lipoprotein (Lpp is involved in inflammatory responses and septic shock. We previously characterized a Δlpp mutant of Yersinia pestis CO92 and found that this mutant was defective in surviving in macrophages and was attenuated in a mouse inhalation model of plague when compared to the highly virulent wild-type (WT bacterium. We performed global transcriptional profiling of WT Y. pestis and its Δlpp mutant using microarrays. The organisms were cultured at 26 and 37 degrees Celsius to simulate the flea vector and mammalian host environments, respectively. Our data revealed vastly different effects of lpp mutation on the transcriptomes of Y. pestis grown at 37 versus 26C. While the absence of Lpp resulted mainly in the downregulation of metabolic genes at 26C, the Y. pestis Δlpp mutant cultured at 37C exhibited profound alterations in stress response and virulence genes, compared to WT bacteria. We investigated one of the stress-related genes (htrA downregulated in the Δlpp mutant relative to WT Y. pestis. Indeed, complementation of the Δlpp mutant with the htrA gene restored intracellular survival of the Y. pestis Δlpp mutant. Our results support a role for Lpp in Y. pestis adaptation to the host environment, possibly via transcriptional activation of htrA.

  3. Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

    Directory of Open Access Journals (Sweden)

    Cristi L. Galindo

    2009-01-01

    Full Text Available We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT Y. pestis CO92 and its Braun lipoprotein (Δlpp mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS- associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague.

  4. Oral administration of a Spirulina extract enriched for Braun-type lipoproteins protects mice against influenza A(H1N1) virus infection

    Science.gov (United States)

    Previous studies indicate that Immulina, a commercial extract of Arthrospira (Spirulina) platensis, is a potent activator of innate immune cells and that Braun-type lipoproteins (a principal toll-like receptor (TLR) 2 ligand) are the main active components within this product. In the present study, ...

  5. Enhancement of natural killer cell activity in healthy subjects by Immulina®, a Spirulina extract enriched for Braun-type lipoproteins

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Balachandran, Premalatha; Christensen, Ole

    2010-01-01

    Immulina®, a commercial extract of Arthrospira (Spirulina) platensis is a potent activator of THP-1 monocytes and CD4+ T cells IN VITRO and enhances several immunological functions in mice. We further characterized Immulina® by determining that Braun-type lipoproteins are responsible for a major ...

  6. Enhancement of natural killer cell activity in healthy subjects by Immulina®, a Spirulina extract enriched for Braun-type lipoproteins

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Balachandran, Premalatha; Christensen, Ole

    2010-01-01

    Immulina®, a commercial extract of Arthrospira (Spirulina) platensis is a potent activator of THP-1 monocytes and CD4+ T cells IN VITRO and enhances several immunological functions in mice. We further characterized Immulina® by determining that Braun-type lipoproteins are responsible for a major...

  7. DETECTING LOW DENSITY LIPOPROTEIN RECEPTOR MUTANT GENE OF RABBIT BY PCR

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Many factors playi mportant roles inthe devel-opment of human atherosclerotic lesions,the lead-ing risk factor for atherosclerosis is familial hyper-cholesterolaemia(FH)[1-2].FHis a genetic diseasecharacterized by a deficiency of receptors for lowdensity lipoprotein(LDL)on the plas malemma ofendothelial cells,a high level of serum LDL,andearly development of atherosclerosis[3].WatanabeHeritable Hyperlipidaemic(WHHL)rabbits withunprovoked hypercholesterolaemia,increased bloodlevel of LDL,pronounced atheroscl...

  8. DETECTING LOW DENSITY LIPOPROTEIN RECEPTOR MUTANT GENE OF RABBIT BY PCR

    Institute of Scientific and Technical Information of China (English)

    Liu Enqi; Zhao Sihai; Chen Zhenglan; Yang Penghui

    2006-01-01

    Objective Watanabe Heritable Hyperlipidaemic (WHHL) rabbits with low density lipoprotein receptor (LDLr) gene mutation have provided unprecedented opportunities for the study of human atherosclerosis, in order to confirm LDL receptor gene status in rabbits, we developed a simple PCR technique to detect LDL mutations in rabbits. Methods Rabbits genomic DNA were extracted from ear biopsy, and amplified by PCR to detect 12 bp deletion mutation in WHHL rabbits. PCR products were directly digested with BglⅠ, and then applied to polyacrylamide gel electrophoresis. Results PCR products from homozygous LDLr +/+ rabbits generated 2 bands of 212 and 94 bp after BglⅠ digestion, LDLr +/- rabbits generated 3 bands (294, 212, and 94 bp), LDLr -/- animals, however, generated only 1 product (294 bp). Conclusion This modified PCR method is simple and reliable.

  9. Dr. von Braun Briefing Walt Disney

    Science.gov (United States)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  10. Walt Disney and Dr. Wernher von Braun

    Science.gov (United States)

    1954-01-01

    Dr. Werhner von Braun, then Chief, Guided Missile Development Operation Division at Army Ballistic Missile Agency (ABMA) in Redstone Arsenal, Alabama, was visited by Walt Disney in 1954. In the 1950's, von Braun worked with Disney Studio as a technical director, making three films about space exploration for television. A model of the V-2 rocket is in background.

  11. Braunes Fettgewebe: Die neue Waffe gegen Adipositas?

    Directory of Open Access Journals (Sweden)

    Fenzl A

    2014-01-01

    Full Text Available Adipositas entsteht, wenn die Energieaufnahme den Energieverbrauch übersteigt. Braunes Fett – im Gegensatz zu weißem Fett – ist darauf ausgerichtet, Energie in Form von Wärmeproduktion (Thermogenese zu verbrauchen. Bei diesem Vorgang wird die Atmungskette von der ATP-Synthese entkoppelt, was durch das Molekül „Uncoupling Protein-1“ (UCP-1 vermittelt wird, welches praktisch nur in braunem Fettgewebe vorkommt. Aufgrund seiner hohen Stoffwechselaktivität und der rezenten Entdeckung, dass aktives braunes Fett auch in Erwachsenen vorkommt, hat dieses Gewebe in den vergangenen Jahren einen hohen Stellenwert in der Adipositasforschung erlangt. In zahlreichen Tiermodellen führt die Aktivierung von braunem Fett oder die Transformation von weißem in braunes Fett (browning zu einer Erhöhung des Energieumsatzes sowie zum Schutz vor Adipositas und metabolischen Komplikationen. Zusätzlich zu klassisch braunem und weißem Fett wurde kürzlich eine neue Fettart beschrieben, die sowohl weiße als auch braune Eigenschaften aufweist – das so genannte „beige“ Fett. Beige Fettzellen kommen zwar primär im weißen Fettgewebe vor, können aber, ähnlich wie braune Adipozyten, thermogenetisch hoch aktiv sein. Es werden laufend neue Faktoren entdeckt, die die Entwicklung und/oder Funktion von beigem bzw. braunem Fett kontrollieren. Die Bemühungen, molekulare Mechanismen und Stoffwechselvorgänge in braunem Fett besser zu verstehen, haben sich noch intensiviert, als man kürzlich mittels FDG-PET-Untersuchungen entdeckte, dass aktives braunes Fettgewebe nicht nur in Erwachsenen vorkommt, sondern auch den Energieverbrauch steigert. Derzeit existieren allerdings noch keine pharmakologischen Ansätze, um die metabolischen Eigenschaften von braunem Fett therapeutisch nutzen zu können, doch das Rennen ist längst im Gange.

  12. Portrait of Dr. Von Braun with Walt Disney, 1954.

    Science.gov (United States)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  13. The odontological identification of Eva Braun Hitler.

    Science.gov (United States)

    Keiser-Nielsen, S; Strøm, F

    1983-01-01

    On May 7th-9th, 1945, a team of Russian pathologists autopsied several bodies found in and near the Fuehrer Bunker in Berlin; among them, a female body (No. 13) was later identified as that of Eva Braun Hitler (EBH), mainly by means of a gold bridge from the lower right jaw. A postmortem photograph of this bridge also shows a separate gold filling. Data now available on the dental treatment of EBH have permitted the present authors to substantiate that this gold filling also came from the mouth of EBH. Further speculation about the fate of EBH would henceforth seem professionally unfounded.

  14. Victor or Villain? Wernher von Braun and the Space Race

    Science.gov (United States)

    O'Brien, Jason L.; Sears, Christine E.

    2011-01-01

    Set during the Cold War and space race, this historical role-play focuses on Wernher von Braun's involvement in and culpability for the use of slave laborers to produce V-2 rockets for Nazi Germany. Students will grapple with two central questions. Should von Braun have been allowed to emigrate to the United States given his affiliation with the…

  15. The two murein lipoproteins of Salmonella enterica serovar Typhimurium contribute to the virulence of the organism.

    Science.gov (United States)

    Sha, J; Fadl, A A; Klimpel, G R; Niesel, D W; Popov, V L; Chopra, A K

    2004-07-01

    Septic shock due to Salmonella and other gram-negative enteric pathogens is a leading cause of death worldwide. The role of lipopolysaccharide in sepsis is well studied; however, the contribution of other bacterial outer membrane components, such as Braun (murein) lipoprotein (Lpp), is not well defined. The genome of Salmonella enterica serovar Typhimurium harbors two copies of the lipoprotein (lpp) gene. We constructed a serovar Typhimurium strain with deletions in both copies of the lpp gene (lpp1 and lpp2) by marker exchange mutagenesis. The integrity of the cell membrane and the secretion of the effector proteins through the type III secretion system were not affected in the lpp double-knockout mutant. Subsequently, the virulence potential of this mutant was examined in a cell culture system using T84 intestinal epithelial and RAW264.7 macrophage cell lines and a mouse model of salmonellosis. The lpp double-knockout mutant was defective in invading and inducing cytotoxic effects in T84 and RAW264.7 cells, although binding of the mutant to the host cell was not affected when compared to the wild-type (WT) serovar Typhimurium. The motility of the mutant was impaired, despite the finding that the number of flagella was similar in the lpp double knockout mutant and the WT serovar Typhimurium. Deletion in the lpp genes did not affect the intracellular survival and replication of Salmonella in macrophages and T84 cells. Induction of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-8 (IL-8) was significantly reduced in macrophages and T84 cells infected with the lpp double-knockout mutant. The levels of IL-8 remained unaffected in T84 cells when infected with either live or heat-killed WT and lpp mutant, indicating that invasion was not required for IL-8 production and that Toll-like receptor 2 signaling might be affected in the Lpp double-knockout mutant. These effects of the Lpp protein could be restored by complementation of the isogenic

  16. Studies on the Formation of Murein-Bound Lipoprotein in Escherichia coli

    Science.gov (United States)

    1992-05-15

    Proteus mirabilis, Morqanella morqanii, Erwinia amylovora and serratia marcescens, and in Pseudomonas aeruqinosa lipoprotein I (Fig. 5., YU, 1987... Erwinia amylovora lipoprotein gene. J. Biol. Chern. 256:2194-2198. Yamaguchi, K., and Inouye, M. (1988). Lipoprotein 28, an inner membrane protein of...et AI., 1983), ~. amylovora (Yamagata et li., 1981) and ~. marcescens (Braun et al., 1970), and in .E. aeruginosa (Mizuno and Kageyama, 1979). Like

  17. Dr. Space the life of Wernher von Braun

    CERN Document Server

    Ward, Bob

    2013-01-01

    Written by veteran aerospace journalist Bob Ward, who spent years investigating his subject, this biography presents a revealing but even-handed portrait of the father of modern rocketry. As he chronicles Wernher von Braun's life, Ward explodes many myths and misconceptions about the controversial genius who was a hero to some, a villain to others. The picture of von Braun that emerges is of a brilliant scientist with limitless curiosity and a drive to achieve his goals at almost any price from, developing the world's first ballistic missile used against the Allies in World War II to help

  18. Some special features of the le chatelier-braun principle

    Science.gov (United States)

    Nesis, E. I.; Skibin, Yu. N.

    2000-07-01

    The relaxation reaction of a system that follows from the Le Chatelier-Braun principle and weakens the result of an external influence turns out to be more intense under a complex action. A method for quantitative determination of the weakening effect for simple and complex actions is suggested.

  19. Braun-Le Chatelier principle in dissipative thermodynamics

    CERN Document Server

    Pavelka, Michal

    2016-01-01

    Braun-Le Chatelier principle is a fundamental result of equilibrium thermodynamics, showing how stable equilibrium states shift when external conditions are varied. The principle follows from convexity of thermodynamic potential. Analogously, from convexity of dissipation potential it follows how steady non-equilibrium states shift when thermodynamic forces are varied, which is the extension of the principle to dissipative thermodynamics.

  20. Wernher von Braun: Reflections on His Contributions to Space Exploration

    Science.gov (United States)

    Goldman, Arthur E.

    2012-01-01

    In 1950, Dr. Wernher von Braun and approximately 100 of his team members came to Huntsville, Alabama, to begin work with the Army on what would later become America's historic space program. He would later serve as the first director of the Marshall Space Flight Center and led the development of the Saturn V launch vehicle that launched seven crewed American mission to the moon, as well as America s first space station, Skylab. Von Braun is best known for his team s technical achievements. He realized his dream of exploring outer space by helping place humans on the moon. His engineering and managerial talent during the Apollo era had contributed to a technological revolution. He was by all accounts a good engineer, but he was only one among many. What set Von Braun apart were his charisma, his vision, and his leadership skills. He inspired loyalty and dedication in the people around him. He understood the importance of communicating his vision to his team, to political and business leaders and the public. Today, the Marshall Center continues his vision by pursuing engineering and scientific projects that will continue to open space to exploration. This presentation will discuss Von Braun's impact on Huntsville, the Marshall Center, the nation and the world and look at his contributions in context of where world space exploration is today.

  1. von Braun Examines Bendix Mobility Test Article (MTA)

    Science.gov (United States)

    1965-01-01

    Marshall Space Flight Center (MSFC) director, Wernher von Braun, and a visitor, examine one concept of a possible Lunar Roving Vehicle (LRV) built by the Bendix Corporation. The data provided by the MTA helped in designing the LRV, developed under the direction of MSFC. The LRV was designed to allow Apollo astronauts a greater range of mobility during lunar exploration missions.

  2. Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection.

    Science.gov (United States)

    Fadl, A A; Sha, J; Klimpel, G R; Olano, J P; Niesel, D W; Chopra, A K

    2005-02-01

    Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased

  3. Dr. von Braun on the Mobility Test Article (MTA)

    Science.gov (United States)

    1966-01-01

    In this June 1966 photograph, Marshall Space Flight Center Director Dr. Wernher von Braun test-drives the Mobility Test Article (MTA), a developmental vehicle built by the Bendix Corporation to test lunar mobility vehicle concepts. The data provided by the MTA helped in designing the Lunar Roving Vehicle (LRV), developed under the direction of the MSFC. The LRV was designed to allow Apollo astronauts a greater range of mobility during lunar exploration missions. The LRVs were deployed during the last three Apollo missions; Apollo 15, Apollo 16, and Apollo 17.

  4. Special Issue on Signal Processing for Mechanical Systems in Honor of Professor Simon Braun

    Science.gov (United States)

    Fassois, Spilios D.

    2016-06-01

    This Special Issue is in honor of a pioneer of the area of Signal Processing for Mechanical Systems and, at the same time, Founding Editor of the Journal of Mechanical Systems and Signal Processing (MSSP), Professor Simon Braun.

  5. A process supported by the utility BBPC for analysing Braun-Blanquet data on a personal computer

    Directory of Open Access Journals (Sweden)

    H. Bezuidenhout

    1996-01-01

    Full Text Available Many South African vegetation scientists use utilise the Braun-Blanquet methodology. The main aim of this paper is to describe an affordable, rapid and efficient process for analysing Braun-Blanquet phytosociological data sets on a personal computer. It describes a suite of utilities joining various phases and this makes the entire process possible.

  6. Dr. Wernher Von Braun greeting dignitaries at the Redstone Arsenal airfield.

    Science.gov (United States)

    1999-01-01

    Dr. George E. Mueller, center, associate administrator for manned space flight, is flanked by Dr. Wernher Von Braun, left, and Dr. Eberhard Rees at the Redstone Arsenal airstrip. the associate adminstrator was making his annual staff visit to the Marshall Space Flight Center.

  7. Lipoprotein(a)

    DEFF Research Database (Denmark)

    Langsted, Anne; Kamstrup, Pia R; Nordestgaard, Børge G

    2014-01-01

    tested whether normal food intake or inflammation influenced lipoprotein(a)'s ability to predict ischemic heart disease. METHODS: We studied 34 829 individuals from the Danish general population using the Copenhagen General Population Study and the Copenhagen City Heart Study. RESULTS: Lipoprotein......(a) levels did not change in response to normal food intake: median fasting levels were 17.3 mg/dL, while median levels at 3-4 h since last meal were 19.4 mg/dL(p = 0.38). Lipoprotein(a) levels increased minimally with increasing levels of C-reactive protein(CRP): median lipoprotein(a) levels at CRP

  8. Glycosaminoglycan-lipoprotein interaction.

    Science.gov (United States)

    Olsson, U; Ostergren-Lundén, G; Moses, J

    2001-10-01

    Glycosaminoglycans (GAGs) bound to various proteoglycans (PGs) present in the cardiovascular system have been proposed to perform a wide range of functions. These include conferring viscoelastic properties; interacting with and modulating growth factors and enzymes; and as receptors and co-receptors in lipoprotein metabolism. Binding of apoB-100 lipoproteins, particularly low density lipoproteins (LDL), to GAGs of extracellular matrix PGs in arteries has been proposed to be an initiating event in development of atherosclerosis. This study was initiated with the aim of getting an overview of the binding patterns of different lipoprotein subclasses with individual GAG categories. We thus evaluated the interaction of lipoproteins with GAGs commonly found in the cardiovascular system using a gel mobility-shift assay developed for this purpose. The same procedure was used to measure lipoproteins binding to metabolically [(35)S]-labeled whole PGs prepared from three cell types, arterial smooth muscle cells, THP-1 macrophages and from HepG2 cells. The effect of GAG composition on PGs on lipoprotein binding was evaluated by enzymatic degradation of the carbohydrate chains. Heparan sulfate was found to bind beta very low density lipoproteins (beta-VLDL) and a chylomicron remnant model (beta-VLDL+apoE), but not LDL. Dermatan sulfate was found to bind LDL, but not beta-VLDL or the chylomicron remnant model. Chondroitin sulfate and heparin were found to bind all lipoproteins tested (LDL, beta-VLDL and beta-VLDL+apoE) although with different affinities. We can conclude that each lipoprotein subclass tested binds a specific assortment of the GAGs tested. The observations made contribute to the understanding of new and complex mechanisms by which carbohydrate and lipid metabolism may be linked.

  9. Billroth II with Braun Enteroenterostomy Is a Good Alternative Reconstruction to Roux-en-Y Gastrojejunostomy in Laparoscopic Distal Gastrectomy

    OpenAIRE

    Long-Hai Cui; Sang-Yong Son; Ho-Jung Shin; Cheulsu Byun; Hoon Hur; Sang-Uk Han; Yong Kwan Cho

    2017-01-01

    Background. Although Billroth II (BII) reconstruction is simpler and faster than Billroth I or Roux-en-Y (RY) reconstruction in patients undergoing totally laparoscopic distal gastrectomy (TLDG), BII reconstruction is associated with several complications, including more severe bile reflux. BII Braun anastomosis may be a better alternative to RY reconstruction. Methods. This retrospective study included 56 consecutive patients who underwent TLDG for gastric cancer, followed by BII Braun or RY...

  10. Werner von Braun relaxes after successful Apollo 11 Saturn V launch

    Science.gov (United States)

    1969-01-01

    Dr. Wernher von Braun, director of the Marshall Space Flight Center, Huntsville, Alabama, relaxes after the successful launch of Apollo 11 astronauts Neil A. Armstrong, Michael Collins and Edwin Aldrin Jr. today. Their historic lunar landing mission began at 9:32 a.m. EDT, July 16, 1969, when an Apollo/Saturn V space vehicle lifted off from the spaceport's Launch Complex 39A.

  11. la teoría del desarrollo desigual de Óscar Braun. Un análisis critico

    Directory of Open Access Journals (Sweden)

    Wright Phil

    1979-12-01

    Full Text Available

    En este análisis crítico de la teoría del intercambio desigual de Oscar Braun, intentamos movernos consistentemente a través de un número de etapas analíticas distintas. Estas etapas son: a una discusión sobre el objeto del conocimiento en Braun, sin las restricciones de su propia problemática (sección 3; b una confrontación del objeto del conocímiento en Braun con el objeto real o concreto (sección4, y c una crítica a] objeto del conocimiento en Braun (secciones 2 y 5. La crítica del objeto del conocimiento en Braun se divide en dos partes ya que tratamos con dos problemas analíticos distintos: a la teoría del intercambio desigual puede estar representada como una teoría del imperialismo, y b la naturaleza del objeto del conocimiento contenida en la teoría del intercambio desigual de Braun es la que causa los problemas y la que lo lleva a constituirla como una teoría del imperialismo.

  12. Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus.

    Directory of Open Access Journals (Sweden)

    Satomi Yamamoto

    2016-05-01

    Full Text Available Scavenger receptor class B type 1 (SR-B1 and low-density lipoprotein receptor (LDLR are known to be involved in entry of hepatitis C virus (HCV, but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV.

  13. Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus.

    Science.gov (United States)

    Yamamoto, Satomi; Fukuhara, Takasuke; Ono, Chikako; Uemura, Kentaro; Kawachi, Yukako; Shiokawa, Mai; Mori, Hiroyuki; Wada, Masami; Shima, Ryoichi; Okamoto, Toru; Hiraga, Nobuhiko; Suzuki, Ryosuke; Chayama, Kazuaki; Wakita, Takaji; Matsuura, Yoshiharu

    2016-05-01

    Scavenger receptor class B type 1 (SR-B1) and low-density lipoprotein receptor (LDLR) are known to be involved in entry of hepatitis C virus (HCV), but their precise roles and their interplay are not fully understood. In this study, deficiency of both SR-B1 and LDLR in Huh7 cells was shown to impair the entry of HCV more strongly than deficiency of either SR-B1 or LDLR alone. In addition, exogenous expression of not only SR-B1 and LDLR but also very low-density lipoprotein receptor (VLDLR) rescued HCV entry in the SR-B1 and LDLR double-knockout cells, suggesting that VLDLR has similar roles in HCV entry. VLDLR is a lipoprotein receptor, but the level of its hepatic expression was lower than those of SR-B1 and LDLR. Moreover, expression of mutant lipoprotein receptors incapable of binding to or uptake of lipid resulted in no or slight enhancement of HCV entry in the double-knockout cells, suggesting that binding and/or uptake activities of lipid by lipoprotein receptors are essential for HCV entry. In addition, rescue of infectivity in the double-knockout cells by the expression of the lipoprotein receptors was not observed following infection with pseudotype particles bearing HCV envelope proteins produced in non-hepatic cells, suggesting that lipoproteins associated with HCV particles participate in the entry through their interaction with lipoprotein receptors. Buoyant density gradient analysis revealed that HCV utilizes these lipoprotein receptors in a manner dependent on the lipoproteins associated with HCV particles. Collectively, these results suggest that lipoprotein receptors redundantly participate in the entry of HCV.

  14. Randomized trial comparing episiotomies with Braun-Stadler episiotomy scissors and EPISCISSORS-60®

    Directory of Open Access Journals (Sweden)

    Sawant G

    2015-06-01

    Full Text Available Ganpat Sawant, Divya Kumar Dr DY Patil Medical College and Hospital, Nerul, Navi Mumbai, India Introduction: Episiotomy angle is a crucial factor in causation of obstetric anal sphincter injuries (OASIS, which are the major cause of female bowel incontinence. Sutured episiotomies angled too close to the midline (<30 degree or too far away from the midline (.60 degree fail to unload the perineum sufficiently and predispose to OASIS. A 25-degree post-delivery episiotomy suture angle has a 10% risk of OASIS while 45-degree episiotomy is associated with 0.5% risk. To account for perineal distension at crowning, a 60-degree episiotomy incision is required to achieve 43–50 degree suture angles. We compared episiotomy suture angles with commonly used Braun-Stadler episiotomy scissors with the new fixed angle EPISCISSORS-60®. Methods: Ethical approval was obtained. A prospective cluster randomization design was chosen. Thirty-one patients were required in each group for a 12-degree difference with power at 90% and 5% significance. Sutured episiotomy angles and post-delivery linear distance from caudal end of the sutured episiotomy to the anus were measured with protractors and rulers. Two-tailed t-tests were used to compare the two groups. Results: Thirty-one nulliparae had episiotomies with EPISCISSORS-60®, 32 with Braun-Stadler. Mean age (25 versus 24.8 years was similar. EPISCISSORS-60® episiotomies were angled 12 degrees more laterally away from the anus compared to Braun-Stadler (40.6 degrees, 95% confidence interval [CI] ±2, interquartile range [IQR] 35–45 versus 28.3 degrees, 95% CI ±2, IQR 25–30, P<0.0001. The post-delivery linear distance from caudal end of the sutured episiotomy to the anus was 15 mm more with the EPISCISSORS-60® compared to Braun-Stadler (35 mm, 95% CI ±2.2, IQR =30–39 versus 19.5; 95% CI ±1.3, IQR =14.75–22.25 P<0.0001. EPISCISSORS-60® episiotomies measured longer (47 mm versus 40 mm, P<0.0001. There were

  15. Randomized trial comparing episiotomies with Braun-Stadler episiotomy scissors and EPISCISSORS-60®

    Science.gov (United States)

    Sawant, Ganpat; Kumar, Divya

    2015-01-01

    Introduction Episiotomy angle is a crucial factor in causation of obstetric anal sphincter injuries (OASIS), which are the major cause of female bowel incontinence. Sutured episiotomies angled too close to the midline (60 degree) fail to unload the perineum sufficiently and predispose to OASIS. A 25-degree post-delivery episiotomy suture angle has a 10% risk of OASIS while 45-degree episiotomy is associated with 0.5% risk. To account for perineal distension at crowning, a 60-degree episiotomy incision is required to achieve 43–50 degree suture angles. We compared episiotomy suture angles with commonly used Braun-Stadler episiotomy scissors with the new fixed angle EPISCISSORS-60®. Methods Ethical approval was obtained. A prospective cluster randomization design was chosen. Thirty-one patients were required in each group for a 12-degree difference with power at 90% and 5% significance. Sutured episiotomy angles and post-delivery linear distance from caudal end of the sutured episiotomy to the anus were measured with protractors and rulers. Two-tailed t-tests were used to compare the two groups. Results Thirty-one nulliparae had episiotomies with EPISCISSORS-60®, 32 with Braun-Stadler. Mean age (25 versus 24.8 years) was similar. EPISCISSORS-60® episiotomies were angled 12 degrees more laterally away from the anus compared to Braun-Stadler (40.6 degrees, 95% confidence interval [CI] ±2, interquartile range [IQR] 35–45 versus 28.3 degrees, 95% CI ±2, IQR 25–30, P<0.0001). The post-delivery linear distance from caudal end of the sutured episiotomy to the anus was 15 mm more with the EPISCISSORS-60® compared to Braun-Stadler (35 mm, 95% CI ±2.2, IQR =30–39 versus 19.5; 95% CI ±1.3, IQR =14.75–22.25 P<0.0001). EPISCISSORS-60® episiotomies measured longer (47 mm versus 40 mm, P<0.0001). There were no OASIS cases in the EPISCISSORS-60® group versus one in the Braun-Stadler group. Conclusion The EPISCISSORS-60® sutured episiotomies are much further away

  16. Subunit II of Bacillus subtilis cytochrome c oxidase is a lipoprotein

    NARCIS (Netherlands)

    Bengtsson, J; Tjalsma, H; Rivolta, C; Hederstedt, L

    1999-01-01

    The sequence of the N-terminal end of the deduced ctaC gene product of Bacillus species has the features of a bacterial lipoprotein. CtaC is the subunit II of cytochrome caa(3), which is a cytochrome c oxidase. Using Bacillus subtilis mutants blocked in lipoprotein synthesis, we show that CtaC is a

  17. Billroth II with Braun Enteroenterostomy Is a Good Alternative Reconstruction to Roux-en-Y Gastrojejunostomy in Laparoscopic Distal Gastrectomy

    Science.gov (United States)

    Cui, Long-Hai; Shin, Ho-Jung; Byun, Cheulsu; Hur, Hoon; Han, Sang-Uk; Cho, Yong Kwan

    2017-01-01

    Background. Although Billroth II (BII) reconstruction is simpler and faster than Billroth I or Roux-en-Y (RY) reconstruction in patients undergoing totally laparoscopic distal gastrectomy (TLDG), BII reconstruction is associated with several complications, including more severe bile reflux. BII Braun anastomosis may be a better alternative to RY reconstruction. Methods. This retrospective study included 56 consecutive patients who underwent TLDG for gastric cancer, followed by BII Braun or RY reconstruction, between January 2013 and December 2015. Surgical outcomes, including length of operation, quantity of blood lost, and postoperative complications, were compared in the two groups. Results. Clinicopathological characteristics did not differ between the BII Braun and RY groups. Mean length of operation was significantly longer in the RY than the BII Braun group (157.3 min versus 134.6 min, p gastritis in the remnant stomach in the two groups. Conclusions. B-II Braun anastomosis is a good alternative to RY reconstruction, reducing length of operation and ileus after TLDG. PMID:28163716

  18. Albert Einstein and Wernher von Braun - the two great German-American physicists seen in a historical perspective.

    Science.gov (United States)

    Winterberg, Friedwardt

    2008-04-01

    It was Albert Einstein who for the first time changed our view of the universe to be a non-euclidean curved space-time. And it was Wernher von Braun who blazed the trail to take us into this universe, leaving for the first time the gravitational field of our planet earth, with the landing a man on the moon the greatest event in human history. Both these great physicists did this on the shoulders of giants. Albert Einstein on the shoulders of his landsman, the mathematician Bernhard Riemann, and Wernher von Braun on the shoulders of Goddard and Oberth. Both Einstein and von Braun made a Faustian pact with the devil, von Braun by accepting research funds from Hitler, and Einstein by urging Roosvelt to build the atom bomb (against Hitler). Both of these great men later regretted the use of their work for the killing of innocent bystanders, even though in the end the invention of nuclear energy and space flight is for the benefit of man. Their example serves as a warning for all of us. It can be formulated as follows: ``Can I in good conscience accept research funds from the military to advance scientific knowledge, for weapons developed against an abstract enemy I never have met in person?'' Weapons if used do not differentiate between the scientist, who invented these weapons, and the non-scientist.

  19. Wernher von Braun Takes a Close Look at Apollo 15 Launch

    Science.gov (United States)

    1971-01-01

    During the Apollo 15 launch activities in the launch control center's firing room 1 at Kennedy Space Center, Dr. Wernher von Braun, NASA's Deputy Associate Administrator for planning, takes a closer look at the launch pad through binoculars. The fifth manned lunar landing mission, Apollo 15 (SA-510), carrying a crew of three astronauts: Mission commander David R. Scott, Lunar Module pilot James B. Irwin, and Command Module pilot Alfred M. Worden Jr., lifted off on July 26, 1971. Astronauts Scott and Irwin were the first to use a wheeled surface vehicle, the Lunar Roving Vehicle, or the Rover, which was designed and developed by the Marshall Space Flight Center, and built by the Boeing Company. Astronauts spent 13 days, nearly 67 hours, on the Moon's surface to inspect a wide variety of its geological features.

  20. Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

    DEFF Research Database (Denmark)

    Roeseler, Eberhard; Julius, Ulrich; Heigl, Franz

    2016-01-01

    OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correl...

  1. Lipoprotein metabolism indicators improve cardiovascular risk prediction

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Graaf, A.A. de; Tsivtsivadze, E.; Parnell, L.D.; Werff-van der Vat, B.J.C. van der; Ommen, B. van; Greef, J. van der; Ordovás, J.M.

    2014-01-01

    Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to inves

  2. Congenital β-lipoprotein deficiency

    NARCIS (Netherlands)

    Buchem, F.S.P. van; Pol, G.; Gier, J. de; Böttcher, C.J.F.; Pries, C.

    1966-01-01

    There are several degrees of β-lipoprotein deficiency. If there is no β-lipoprotein present, or if there are only traces of it, the Bassen-Kornzweig syndrome develops. A constant feature of this syndrome is disturbed fat absorption with accumulation of fat in the epithelium of intestinal mucosa and

  3. Physiological regulation of lipoprotein lipase

    NARCIS (Netherlands)

    Kersten, A.H.

    2014-01-01

    The enzyme lipoprotein lipase (LPL), originally identified as the clearing factor lipase, hydrolyzes triglycerides present in the triglyceride-rich lipoproteins VLDL and chylomicrons. LPL is primarily expressed in tissues that oxidize or store fatty acids in large quantities such as the heart, skele

  4. The ppm operon is essential for acylation and glycosylation of lipoproteins in Corynebacterium glutamicum.

    Directory of Open Access Journals (Sweden)

    Niloofar Mohiman

    Full Text Available BACKGROUND: Due to their contribution to bacterial virulence, lipoproteins and members of the lipoprotein biogenesis pathway represent potent drug targets. Following translocation across the inner membrane, lipoprotein precursors are acylated by lipoprotein diacylglycerol transferase (Lgt, cleaved off their signal peptides by lipoprotein signal peptidase (Lsp and, in Gram-negative bacteria, further triacylated by lipoprotein N-acyl transferase (Lnt. The existence of an active apolipoprotein N-acyltransferase (Ms-Ppm2 involved in the N-acylation of LppX was recently reported in M. smegmatis. Ms-Ppm2 is part of the ppm operon in which Ppm1, a polyprenol-monophosphomannose synthase, has been shown to be essential in lipoglycans synthesis but whose function in lipoprotein biosynthesis is completely unknown. RESULTS: In order to clarify the role of the ppm operon in lipoprotein biosynthesis, we investigated the post-translational modifications of two model lipoproteins (AmyE and LppX in C. glutamicum Δppm1 and Δppm2 mutants. Our results show that both proteins are anchored into the membrane and that their N-termini are N-acylated by Cg-Ppm2. The acylated N-terminal peptide of LppX was also found to be modified by hexose moieties. This O-glycosylation is localized in the N-terminal peptide of LppX and disappeared in the Δppm1 mutant. While compromised in the absence of Cg-Ppm2, LppX O-glycosylation could be restored when Cg-Ppm1, Cg-Ppm2 or the homologous Mt-Ppm1 of M. tuberculosis was overexpressed. CONCLUSION: Together, these results show for the first time that Cg-Ppm1 (Ppm synthase and Cg-Ppm2 (Lnt operate in a common biosynthetic pathway in which lipoprotein N-acylation and glycosylation are tightly coupled.

  5. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Helena Gylling

    2015-09-01

    Full Text Available The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein

  6. Floral and Seed Variability Patterns among Ethiopian Mustard (B. carinata A. Braun of East Africa

    Directory of Open Access Journals (Sweden)

    Adeniji, OT.

    2012-01-01

    Full Text Available In East Africa, Ethiopian mustard (Brassica carinata A. Braun is cultivated primarily for its leaves, but in Ethiopia preference is high for oil in the seed. Dual purpose importance of the seeds for planting and for oil suggests the need to improve seed production efficiency through understanding variation pattern for floral morphology and seed characters. We investigated genetic diversity and correlations for floral and seed characteristics among 14 accessions of Ethiopian mustard to improve seed set and yield. Field trials were conducted during 2008 and 2009; flowers were examined for short stamen height, long stamen height, pistil height, and silliqua for seed weight, seeds/silliqua and silliqua/plant. Results were largely consistent between years, indicating that the variation measured was mainly controlled by genetic factors. High genetic variation for seed characters and reproductive phenology among the accessions was noted. The number of days to appearance of flowers showed high discriminatory ability among the accessions. A wide continuous variation was observed among accessions for anther-stigma separation. Accessions 1, 3 and 14 were identified as early flowering. A significant and positive correlation coefficient between short stamen height and seed weight indicated a substantial complementation among these characters for seed yield improvement. The short stamen height is a good indicator for selection in favour of seed commercialization and indices for selection of pollen parent for seed yield improvement. Accessions 5, 7, 14, 16 and 22 are best for multiple characters and are recommended for seed production for any of the seasons in Arusha, Tanzania.

  7. Classifying lipoproteins based on their polar profiles.

    Science.gov (United States)

    Polanco, Carlos; Castañón-González, Jorge Alberto; Buhse, Thomas; Uversky, Vladimir N; Amkie, Rafael Zonana

    2016-01-01

    The lipoproteins are an important group of cargo proteins known for their unique capability to transport lipids. By applying the Polarity index algorithm, which has a metric that only considers the polar profile of the linear sequences of the lipoprotein group, we obtained an analytical and structural differentiation of all the lipoproteins found in UniProt Database. Also, the functional groups of lipoproteins, and particularly of the set of lipoproteins relevant to atherosclerosis, were analyzed with the same method to reveal their structural preference, and the results of Polarity index analysis were verified by an alternate test, the Cumulative Distribution Function algorithm, applied to the same groups of lipoproteins.

  8. Aerosol preparation of intact lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Benner, W. Henry (Danville, CA); Krauss, Ronald M (Berkeley, CA); Blanche, Patricia J (Berkeley, CA)

    2012-01-17

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  9. Ion mobility analysis of lipoproteins

    Science.gov (United States)

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2007-08-21

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  10. Resultados neonatais no parto vaginal espontâneo comparados aos dos partos com fórcipe de Simpson-Braun em primíparas

    OpenAIRE

    Pereira,Belmiro Gonçalves; Camargo, Michel Gardere; Couto,Egle Cristina; Amaral, Eliana; Passini Jr,Renato; Parpinelli, Mary Angela

    2004-01-01

    OBJETIVO: comparar os resultados neonatais dos partos vaginais espontâneos ou assistidos com fórcipe de Simpson-Braun em nulíparas. MÉTODO: em estudo de corte retrospectivo foram avaliados dois grupos de primíparas atendidas no Centro Obstétrico do CAISM/UNICAMP, que tiveram parto vaginal sob analgesia epidural. O grupo fórcipe foi formado por 119 pacientes que tiveram parto a fórcipe de Simpson-Braun, e o grupo normal por 114 casos de parto vaginal espontâneo. Foram estudadas as variáveis ne...

  11. Transendothelial lipoprotein exchange and microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Jensen, Kurt Svarre

    2004-01-01

    . METHODS: Using an in vivo isotope technique, transendothelial exchange of low density lipoprotein (LDL) was measured in 77 non-diabetic individuals. Autologous 131-iodinated LDL was reinjected intravenously, and the 1-h fractional escape rate was calculated as index of transendothelial exchange. RESULTS...... transformed) plasma insulin: beta=0.6 (95% CI: 0.1-1.1); R=0.22; P

  12. Butter, margarine and serum lipoproteins.

    NARCIS (Netherlands)

    Zock, P.L.; Katan, M.B.

    1997-01-01

    Intake of trans fatty acids unfavorably affects blood lipoproteins. As margarines are a major source of trans, claims for the advantages of margarines over butter need to be scrutinized. Here we review dietary trials that directly compared the effects of butter and margarine on blood lipids. We iden

  13. Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations as compared with soy protein1-3

    DEFF Research Database (Denmark)

    Nilausen, Karin Johanne; Meinertz, H.

    1999-01-01

    Lipoprotein(a), plasma lipoproteins, dietary proteins, soy protein, casein, liquid-formula, coronary artery disease, men, Denmark......Lipoprotein(a), plasma lipoproteins, dietary proteins, soy protein, casein, liquid-formula, coronary artery disease, men, Denmark...

  14. [Lipoprotein receptors. Old acquaintances and newcomers].

    Science.gov (United States)

    Ducobu, J

    1997-02-01

    Lipoprotein receptors are plasma membrane proteins of high affinity which interact with circulating lipoprotein particles. The well characterized LDL receptor continues to be analysed and some new findings on its intracellular mechanisms of action have emerged. New lipoprotein receptors have recently been described: the chylomicron remnant receptor or LDL-related protein (LRP), the lipolysis stimulated receptor (LSR), the very low density lipoprotein receptor (VLDLR), the HDL receptor (HDLR) and the scavenger receptor (SR). The molecular details of the receptors will facilitate the development of new therapeutic means to improve receptor-mediated clearance of lipoproteins.

  15. Effects of hormones on lipids and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.

    1991-12-01

    Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men and are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.

  16. Comparative testing of drill bits used at the KHS-2 coal plow of Messrs. Halbach-Braun. Vergleichsversuche der am Hobel KHS-2 der Firma Halbach-Braun eingesetzten Hobelmeissel

    Energy Technology Data Exchange (ETDEWEB)

    Klich, A.; Krauze, K.; Podsiadlo, A.; Ptak, J. (Akademia Gorniczo-Hutnicza, Krakow (Poland))

    1990-06-01

    The KHS-2 coal plows of Messrs. Halbach-Braun used in the Polish black coal mine 'Brzeszcze' frequently experienced chain rupture, destruction of the guiding devices for discs and heavy wear of intermediate and ground drill bits that stemmed from the too short service-life of cutting devices and high winning resistance at individual drill bits. In order to remedy these drawbacks, the cutting devices were modified. With the original German, and the modified Polish drill bits, both laboratory and operating tests were carried out. The experimental results reported clearly conform to expectations on the design and technological modifications. The modified drill bits not only have a longer service life because they can be regenerated several times; they also consume less energy. (MOS).

  17. A vegetation survey of the Cape of Good Hope Nature Reserve. I. The use of association-analysis and Braun-Blanquet methods*

    Directory of Open Access Journals (Sweden)

    H. C. Taylor

    1984-12-01

    Full Text Available The survey aimed to establish broad vegetation units that could be mapped on an extensive scale in the Cape of Good Hope Nature Reserve at the southern tip of the Cape Peninsula. This paper compares the performance of two methods, association-analysis and the Braun-Blanquet method as developed by the Zurich-Montpellier School of Phytosociology. One hundred 50 m2  sample plots, covering the whole Reserve, were placed systematically at grid intersections on the 1:18 000 topographical map. at 1 000-yard (914 m intervals. Species lists, recording merely presence of all species with permanently recognizable aerial parts, were made for each plot. The association-analysis resulted in a classification of 23 final groups of sample plots, of which only five groups showed high floristic and ecological homogeneity. Of the remainder, eight groups contained some anomalous, misplaced plots, and ten represented small, isolated fragments of natural units. The original data were then analysed using Braun-Blanquet methods to provide an independent classification for comparison with the former. The Braun-Blanquet communities were found to be more homogeneous in terms of previously defined habitat groupings and showed floristic relationships consistent with these groupings. It is concluded that, with the type of sampling used, the synthetic phytosociological Braun-Blanquet method provides a more natural classification of plant communities of the Reserve than does the monothetic divisive association-analysis method.

  18. Resultados neonatais no parto vaginal espontâneo comparados aos dos partos com fórcipe de Simpson-Braun em primíparas Neonatal outcome of spontaneous deliveries as compared to Simpson-Braun forceps deliveries in nulliparous women

    OpenAIRE

    Belmiro Gonçalves Pereira; Michel Gardere Camargo; Egle Cristina Couto; Eliana Amaral; Renato Passini Jr; Mary Angela Parpinelli

    2004-01-01

    OBJETIVO: comparar os resultados neonatais dos partos vaginais espontâneos ou assistidos com fórcipe de Simpson-Braun em nulíparas. MÉTODO: em estudo de corte retrospectivo foram avaliados dois grupos de primíparas atendidas no Centro Obstétrico do CAISM/UNICAMP, que tiveram parto vaginal sob analgesia epidural. O grupo fórcipe foi formado por 119 pacientes que tiveram parto a fórcipe de Simpson-Braun, e o grupo normal por 114 casos de parto vaginal espontâneo. Foram estudadas as variáveis ne...

  19. Diagnostic markers based on a computational model of lipoprotein metabolism

    NARCIS (Netherlands)

    Schalkwijk, D.B. van; Ommen, B. van; Freidig, A.P.; Greef, J. van der; Graaf, A.A. de

    2011-01-01

    Abstract Background: Dyslipidemia is an important risk factor for cardiovascular disease and type II diabetes. Lipoprotein diagnostics, such as LDL cholesterol and HDL cholesterol, help to diagnose these diseases. Lipoprotein profile measurements could improve lipoprotein diagnostics, but interpreta

  20. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    NARCIS (Netherlands)

    Kersten, A.H.

    2008-01-01

    Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that

  1. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Sander Kersten

    2008-01-01

    Full Text Available Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs. Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels.

  2. The iron-regulated staphylococcal lipoproteins

    Directory of Open Access Journals (Sweden)

    Jessica eSheldon

    2012-04-01

    Full Text Available Lipoproteins fulfill diverse roles in antibiotic resistance, adhesion, protein secretion, signaling and sensing, and many also serve as the substrate binding protein (SBP partner to ABC transporters for the acquisition of a diverse array of nutrients including peptides, sugars, and scarcely abundant metals. In the staphylococci, the iron-regulated SBPs are significantly upregulated during iron starvation and function to sequester and deliver iron into the bacterial cell, enabling staphylococci to circumvent iron restriction imposed by the host environment. Accordingly, this subset of lipoproteins has been implicated in staphylococcal pathogenesis and virulence. Lipoproteins also activate the host innate immune response, triggered through Toll-like receptor-2 (TLR2 and, notably, the iron-regulated subset of lipoproteins are particularly immunogenic. In this review, we discuss the iron-regulated staphylococcal lipoproteins with regard to their biogenesis, substrate specificity, and impact on the host innate immune response.

  3. The pathophysiology of intestinal lipoprotein production

    Directory of Open Access Journals (Sweden)

    Antonina eGiammanco

    2015-03-01

    Full Text Available Intestinal lipoprotein production is a multistep process, essential for the absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins in the endoplasmic reticulum with the formation of primordial, phospholipids-rich particles that are then transported to the Golgi for secretion. Several classes of transporters play a role in the selective uptake and/or export of lipids through the villus enterocytes. Once secreted in the lymph stream, triglyceride-rich lipoproteins (TRLs are metabolized by Lipoprotein lipase (LPL, which catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins (VLDLs and chylomicrons, thereby delivering free fatty acids to various tissues. Genetic mutations in the genes codifying for these proteins are responsible of different inherited disorders affecting chylomicron metabolism.This review focuses on the molecular pathways that modulate the uptake and the transport of lipoproteins of intestinal origin and it will highlight recent findings on TRLs assembly.

  4. Accuracies of the empirical theories of the escape probability based on Eigen model and Braun model compared with the exact extension of Onsager theory.

    Science.gov (United States)

    Wojcik, Mariusz; Tachiya, M

    2009-03-14

    This paper deals with the exact extension of the original Onsager theory of the escape probability to the case of finite recombination rate at nonzero reaction radius. The empirical theories based on the Eigen model and the Braun model, which are applicable in the absence and presence of an external electric field, respectively, are based on a wrong assumption that both recombination and separation processes in geminate recombination follow exponential kinetics. The accuracies of the empirical theories are examined against the exact extension of the Onsager theory. The Eigen model gives the escape probability in the absence of an electric field, which is different by a factor of 3 from the exact one. We have shown that this difference can be removed by operationally redefining the volume occupied by the dissociating partner before dissociation, which appears in the Eigen model as a parameter. The Braun model gives the escape probability in the presence of an electric field, which is significantly different from the exact one over the whole range of electric fields. Appropriate modification of the original Braun model removes the discrepancy at zero or low electric fields, but it does not affect the discrepancy at high electric fields. In all the above theories it is assumed that recombination takes place only at the reaction radius. The escape probability in the case when recombination takes place over a range of distances is also calculated and compared with that in the case of recombination only at the reaction radius.

  5. Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

    Science.gov (United States)

    Biggerstaff, Kyle D.; Wooten, Joshua S.

    2004-01-01

    A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than…

  6. Roles of the protruding loop of factor B essential for the localization of lipoproteins (LolB) in the anchoring of bacterial triacylated proteins to the outer membrane.

    Science.gov (United States)

    Hayashi, Yumi; Tsurumizu, Ryoji; Tsukahara, Jun; Takeda, Kazuki; Narita, Shin-ichiro; Mori, Makiko; Miki, Kunio; Tokuda, Hajime

    2014-04-11

    The Lol system comprising five Lol proteins, LolA through LolE, sorts Escherichia coli lipoproteins to outer membranes. The LolCDE complex, an ATP binding cassette transporter in inner membranes, releases outer membrane-specific lipoproteins in an ATP-dependent manner, causing formation of the LolA-lipoprotein complex in the periplasm. LolA transports lipoproteins through the periplasm to LolB on outer membranes. LolB is itself a lipoprotein anchored to outer membranes, although the membrane anchor is functionally dispensable. LolB then localizes lipoproteins to outer membranes through largely unknown mechanisms. The crystal structure of LolB is similar to that of LolA, and it possesses a hydrophobic cavity that accommodates acyl chains of lipoproteins. To elucidate the molecular function of LolB, a periplasmic version of LolB, mLolB, was mutagenized at various conserved residues. Despite the lack of acyl chains, most defective mutants were insoluble. However, a derivative with glutamate in place of leucine 68 was soluble and unable to localize lipoproteins to outer membranes. This leucine is present in a loop protruding from mLolB into an aqueous environment, and no analogous loop is present in LolA. Thus, leucine 68 was replaced with other residues. Replacement by acidic, but not hydrophobic, residues generated for the first time mLolB derivatives that can accept but cannot localize lipoproteins to outer membranes. Moreover, deletion of the leucine with neighboring residues impaired the lipoprotein receptor activity. Based on these observations, the roles of the protruding loop of LolB in the last step of lipoprotein sorting are discussed.

  7. Computational models for analyzing lipoprotein profiles

    NARCIS (Netherlands)

    Graaf, A.A. de; Schalkwijk, D.B. van

    2011-01-01

    At present, several measurement technologies are available for generating highly detailed concentration-size profiles of lipoproteins, offering increased diagnostic potential. Computational models are useful in aiding the interpretation of these complex datasets and making the data more accessible f

  8. Resultados neonatais no parto vaginal espontâneo comparados aos dos partos com fórcipe de Simpson-Braun em primíparas Neonatal outcome of spontaneous deliveries as compared to Simpson-Braun forceps deliveries in nulliparous women

    Directory of Open Access Journals (Sweden)

    Belmiro Gonçalves Pereira

    2004-02-01

    Full Text Available OBJETIVO: comparar os resultados neonatais dos partos vaginais espontâneos ou assistidos com fórcipe de Simpson-Braun em nulíparas. MÉTODO: em estudo de corte retrospectivo foram avaliados dois grupos de primíparas atendidas no Centro Obstétrico do CAISM/UNICAMP, que tiveram parto vaginal sob analgesia epidural. O grupo fórcipe foi formado por 119 pacientes que tiveram parto a fórcipe de Simpson-Braun, e o grupo normal por 114 casos de parto vaginal espontâneo. Foram estudadas as variáveis neonatais imediatas como o estado do líquido amniótico e os índices de Apgar, assim como a evolução neonatal nos primeiros dias de vida. Para análise estatística foram utilizados os testes c², exato de Fisher e t de Student para comparação de médias e considerada significativa a diferença correspondente a pPURPOSE: to compare maternal and neonatal outcomes between spontaneous vaginal and Simpson-Braun forceps deliveries in nulliparous women. METHOD: a retrospective study including two groups of nulliparous women, who had vaginal delivery under peridural anesthesia in the obstetric unit of the CAISM-UNICAMP: the forceps group included 119 women who had Simpson-Braun forceps delivery, and the normal group included 114 women who delivered spontaneously. Neonatal outcomes, such as Apgar score and the evolution in the first days of life, were studied. Data were compared in both groups and, for statistical analysis, c² test, Fisher exact, and Student t tests were used. The differences were considered significant when p<0.05. RESULTS: the indications for Simpson-Braun forceps delivery were maternal-fetal relief (90 cases and abbreviation of the expulsive period (29 cases. In the forceps group there were 8 cases (6.7% of vaginal injuries; a similar result was observed in the normal group. The number of hospitalization days for the parturient and the newborns was identical, 2.4 days. The newborns in the two groups had similar Apgar scores

  9. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne;

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  10. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...... of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease....

  11. Response functions of the Andersson-Braun and extended range rem counters for neutron energies from thermal to 10 GeV

    CERN Document Server

    Mares, V; Schraube, H

    2002-01-01

    This work is devoted to the calculation of responses as functions of neutron energy for a paired set of Andersson-Braun rem counters, which is commercially available. Different Monte Carlo codes such as MCNP, LAHET, HADRON and MCNPX were applied in the calculations. The study extended to frontal, lateral and isotropic neutron incidence. For an estimation of the contribution of charged high-energy particles to the reading, the responses to protons and pions were also determined. The results obtained give good bases for the practical use of the new instrument in high-energy neutron fields.

  12. Pathology and first report of natural infections of the eye trematode Philophthalmus lachrymosus Braun, 1902 (Digenea, Philophthalmidae in a non-human mammalian host

    Directory of Open Access Journals (Sweden)

    Roberto Magalhães Pinto

    2005-10-01

    Full Text Available The avian eye trematode Philophthalmus lachrymosus Braun, 1902 is for the first time referred naturally occurring in a non-human mammalian host. Previously, natural infections with P. lachrymosus and other species of Philophthalmus have been occasionally reported from man, with few data on experimental infections of non-human mammals. Results presented here are related to the report of two cases of philophthalmosis due to natural infections of wild Brazilian capybaras, Hydrochaeris hydrochaeris L., 1766 with P. lachrymosus and associated pathology. Clinical signs, gross and microscopic lesions as well as new morphometric data on the parasite are presented.

  13. Current situation of lipoprotein apheresis in Saxony.

    Science.gov (United States)

    Julius, U; Taseva, K; Fischer, S; Passauer, J; Bornstein, S R

    2013-01-01

    This paper summarizes the situation pertinent to treatment via lipoprotein apheresis in the federal state of Saxony, Germany in 2010. In total, 119 predominately male patients were treated in 10 centers; the majority of the patients was older than the mean age of the general population. Several risk factors were present, particularly a familial predisposition and hypertension. All patients had experienced cardiovascular events and the majority was taking statins. Patient data from the University Hospital Carl Gustav Carus in Dresden concurred with data derived from patients treated at nephrological practices. In the mean, patients attended the centers for about 6 years, the majority weekly. LDL cholesterol concentrations prior to apheresis were clearly higher than target levels; apheresis sessions decreased LDL cholesterol by 69%. Lipoprotein(a) levels could be measured in 75 patients and were effectively reduced by lipoprotein apheresis. In Saxony, 29 patients per 1 million inhabitants received lipoprotein apheresis, which is higher than the proportion of patients treated in Germany as a whole. The need for this extracorporeal treatment seems to be much greater than its current utilization. Among the patients only one homozygous patient with familial hypercholesterolemia was observed. Physicians should be actively informed about this therapeutic possibility to reduce the cardiovascular risk efficiently. The introduction of new drugs may alter the position of lipoprotein apheresis within the therapeutic spectrum.

  14. THE CHARACTERISATION OF FUNGI Passalora fulva (Cooke U.Braun&Crous PATHOTYPES, CAUSER OF TOMATO LEAF MOLD IN CROATIA

    Directory of Open Access Journals (Sweden)

    Adrijana Novak

    2012-12-01

    Full Text Available Tomato is considered one of the most widely grown vegetable crops in the world and production of it is rising every year in Croatia as well as in the world. This research paper shows results on tomato leaf mould caused by Passalora fulva (Cooke U.Braun & Crous (syn. Cladosporium fulvum (Cooke, which can cause significant reduction of yield and quality of tomato. Other than economic loss, tomato leaf mould can be the cause of allergies because it produces lots of spores. During research, the following materials and methods have been used: collecting samples of plant material infected with tomato leaf mould and assessments of disease intensity, isolation and determination of the pathogen, detecting pathotypes using biassay, susceptibility testing of different tomato genotypes infected with P. fulva, molecular identification and testing the effects of essential oils in vitro on conidia germination. Visual controls of greenhouse and outdoor growing tomato were conducted during the period from 2006 to 2011. Samples (17 from 14 localities in 10 counties (Istra County, Koprivnica-Križevci County, KrapinaZagorje County, Međimurje County, Osijek-BaranjaCounty, Primorje-Gorski Kotar County, Varaždin County, Virovitica-Podravina County, Zadar County and Zagreb County were collected. Symptoms were detected on 6 different tomato genotypes: Belle, Jeremy, Minaret, Amaneta, Gravitet and test genotype. Outdoors, P. fulva was not found. For isolation and determination of P. fulva 4 different growing media were used: PDA (potato – dextrose agar, tomato – agar, carrot – agar and V8 – agar. By measuring the size of conidia on carrot – agar it was determined that they were the closest in size to the conidia from infected tomato leaf. Bioassay for the first time in Croatia confirmed presence of two different physiological pathotypes of P. fulva, Cf – 0 and Cf – 5. Other pathotypes obtained by bioassay were not confirmed by sequencing because the

  15. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut;

    2005-01-01

    CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present......, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis. DESIGN: The study was cross-sectional and was performed in 1999-2002. SETTING: The study took place in the referral center. PATIENTS: The patients included 60 with diabetes mellitus (27 with type 1 diabetes and 33...... with type 2 diabetes) and 42 healthy controls. All were randomly recruited. MAIN OUTCOME MEASURE: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL). Autologous 131I-LDL was reinjected iv, and the 1-h fractional escape rate was taken as an index...

  16. Immune response to lipoproteins in atherosclerosis.

    Science.gov (United States)

    Samson, Sonia; Mundkur, Lakshmi; Kakkar, Vijay V

    2012-01-01

    Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  17. Selective association of outer surface lipoproteins with the lipid rafts of Borrelia burgdorferi.

    Science.gov (United States)

    Toledo, Alvaro; Crowley, Jameson T; Coleman, James L; LaRocca, Timothy J; Chiantia, Salvatore; London, Erwin; Benach, Jorge L

    2014-03-11

    Borrelia burgdorferi contains unique cholesterol-glycolipid-rich lipid rafts that are associated with lipoproteins. These complexes suggest the existence of macromolecular structures that have not been reported for prokaryotes. Outer surface lipoproteins OspA, OspB, and OspC were studied for their participation in the formation of lipid rafts. Single-gene deletion mutants with deletions of ospA, ospB, and ospC and a spontaneous gene mutant, strain B313, which does not express OspA and OspB, were used to establish their structural roles in the lipid rafts. All mutant strains used in this study produced detergent-resistant membranes, a common characteristic of lipid rafts, and had similar lipid and protein slot blot profiles. Lipoproteins OspA and OspB but not OspC were shown to be associated with lipid rafts by transmission electron microscopy. When the ability to form lipid rafts in live B. burgdorferi spirochetes was measured by fluorescence resonance energy transfer (FRET), strain B313 showed a statistically significant lower level of segregation into ordered and disordered membrane domains than did the wild-type and the other single-deletion mutants. The transformation of a B313 strain with a shuttle plasmid containing ospA restored the phenotype shared by the wild type and the single-deletion mutants, demonstrating that OspA and OspB have redundant functions. In contrast, a transformed B313 overexpressing OspC neither rescued the FRET nor colocalized with the lipid rafts. Because these lipoproteins are expressed at different stages of the life cycle of B. burgdorferi, their selective association is likely to have an important role in the structure of prokaryotic lipid rafts and in the organism's adaptation to changing environments. IMPORTANCE Lipid rafts are cholesterol-rich clusters within the membranes of cells. Lipid rafts contain proteins that have functions in sensing the cell environment and transmitting signals. Although selective proteins are present in

  18. Rapid characterization of disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene by overexpression in COS cells

    DEFF Research Database (Denmark)

    Jensen, T G; Andresen, B S; Jensen, H K;

    1996-01-01

    To characterize disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene, COS cells are transfected with the mutant gene in an EBV-based expression vector and characterized by flow cytometry. Using antibodies against the LDL-receptor the amount of receptor protein on the cell...

  19. Lipoprotein apheresis for the treatment of elevated circulating levels of lipoprotein(a): a critical literature review

    Science.gov (United States)

    Franchini, Massimo; Capuzzo, Enrico; Liumbruno, Giancarlo M.

    2016-01-01

    Lipoprotein(a), which consists of a low-density lipoprotein (LDL) particle linked to an apolipoprotein(a) moiety, is currently considered an independent risk factor for cardiovascular disease due to its atherogenic (LDL-like) and prothrombotic (plasminogen-like) properties. The aim of this review is to provide an overview of the current and newer therapies for lowering increased lipoprotein(a) levels, focusing on lipoprotein apheresis. After a systematic literature search, we identified ten studies which, overall, documented that lipoprotein apheresis is effective in reducing increased lipoprotein(a) levels and cardiovascular events. PMID:26710351

  20. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such gene......To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...

  1. Analysis of individual lipoproteins and liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, D.L.; Keller, R.A.; Nolan, J.P. [and others

    1997-08-01

    We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.

  2. Lipoprotein lipase isoelectric point isoforms in humans

    DEFF Research Database (Denmark)

    Badia-Villanueva, M.; Carulla, P.; Carrascal, M.

    2014-01-01

    Lipoprotein lipase (LPL) hydrolyzes circulating triacylglycerols (TAG) into free fatty acids and glycerol. It is present in almost all tissues and its tissue-specific regulation directs the flow of circulating TAG in the body. We demonstrated in a previous study that, in rat heart and post-hepari...

  3. Metabolism of high density lipoproteins in liver cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Ning Xu; Chang-Ping Wu

    2007-01-01

    Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.

  4. Effect of apolipoprotein E variants on lipolysis of very low density lipoproteins by heparan sulphate proteoglycan-bound lipoprotein lipase

    NARCIS (Netherlands)

    Man, F.H.A.F. de; Beer, F. de; Laarse, A. van der; Smelt, A.H.M.; Leuven, J.A.G.; Havekes, L.M.

    1998-01-01

    Lipoprotein lipase (LPL) is bound to heparan sulphate proteoglycans (HSPG) at the luminal surface of endothelium. It is the key enzyme involved in the hydrolysis of very low density lipoproteins (VLDL). Prior to lipolysis by LPL, the lipoproteins are considered to interact with vessel wall HSPG. Apo

  5. Binding of anthracycline derivatives to human serum lipoproteins.

    Science.gov (United States)

    Chassany, O; Urien, S; Claudepierre, P; Bastian, G; Tillement, J P

    1994-01-01

    The binding of eight anthracycline analogues (including mitoxantrone) to isolated serum lipoproteins (high, low and very low density lipoproteins) was studied in order to elucidate some determinants of their interaction with lipidic structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding experiments were run by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by HPLC with fluorometric detection. All the ligands were significantly bound to the three lipoprotein classes, and for each ligand the binding increased as the lipidic fraction of lipoprotein increased. From doxorubicin to iododoxorubicin, there was a tenfold increase in lipoprotein binding (doxorubicin < mitoxantrone < epirubicin < daunorubicin < pirarubicin < aclarubicin < zorubicin < iododoxorubicin). For all the ligands studied, the extent of lipoprotein binding appears to be related to chemical determinants of lipophilicity.

  6. Paragonimus y paragonimiasis en el norte peruano. Infección natural de Pseudothelphusa chilensis por metacercarias de Paragonimus Braun, 1899

    Directory of Open Access Journals (Sweden)

    César Cuba

    2014-06-01

    Full Text Available Se ha estudiado el índice de infección natural y la intensidad del parasitismo en cangrejos recolectados en tres provincias del Departamento de Cajamarca, Perú, habiéndose encontrado metacercarias de Paragonimus Braun, 1899 en el 43.97% de 539 especímenes de Pseudothelphusa chilensis Milne Edwards, 1843, único cangrejo hallado en la zona. El órgano parasitado fue casi exclusivamente el hepatopancreas, siendo 10.33 el número promedio de metacercarias por cangrejo. Las formas adultos logradas mediante inoculación de las metacercarias, fueron identificadas como Paragonimus peruvianus Miyazaki, Ibáñez y Miranda, 1969, con excepción de tres ejemplares que correspondieron a lo especie Paragonimus caliensis Little, 1968.

  7. Sortilins: new players in lipoprotein metabolism

    DEFF Research Database (Denmark)

    Willnow, Thomas; Kjølby, Mads Fuglsang; Nykjær, Anders

    2011-01-01

    PURPOSE OF REVIEW: Sortilins are sorting receptors that direct proteins through secretory and endocytic pathways of the cell. Previously, these receptors have been shown to play important roles in regulating protein transport in neurons and to control neuronal viability and death in many diseases...... of the nervous system. Recent data, including genome-wide association studies, now suggest equally important functions for sortilins in control of systemic lipoprotein metabolism and risk of cardiovascular disease. This review discusses the evidence implicating two members of this gene family, sortilin and SORLA...... on the importance of sorting receptors in control of cellular and systemic lipoprotein metabolism and how altered trafficking pathways may represent a major risk factor for dyslipidemia and atherosclerosis in the human population....

  8. Mycoplasma lipoproteins and Toll-like receptors

    Institute of Scientific and Technical Information of China (English)

    Ling-ling ZUO; Yi-mou WU; Xiao-xing YOU

    2009-01-01

    Mycoplasmas, the smallest free-living, self-replicating bacteria with diameters of 200 to 800 nm, have been reported to be associated with human diseases. It is well known that the mycoplasma lipoprotein/peptide is able to modulate the host immune system, whose N-terminal structure is an important factor in inducing immunity and distinguishing Toll-like receptors (TLRs). However, there is still no clear elucidation about the pathogenic mechanism of mycoplasma lipoprotein/peptide and the signaling pathway. Some researchers have focused on understanding the structures of these proteins and the relationships between their structure and biological function. This review provides an update on the research in this field.

  9. Lipoprotein secretion: It takes two to TANGO.

    Science.gov (United States)

    Pfeffer, Suzanne R

    2016-05-09

    An unsolved mystery in cell biology is how unusually large secretory cargoes are exported from the endoplasmic reticulum. In this issue, Santos et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201603072) report the function of a Mia2/cTAGE5 transcript fusion, named TALI, in the endoplasmic reticulum export of chylomicrons and very low-density lipoproteins, but not collagen XII.

  10. Lipoprotein lipase deficiency with visceral xanthomas

    Energy Technology Data Exchange (ETDEWEB)

    Servaes, Sabah; Bellah, Richard [Department of Radiology, Philadelphia, PA (United States); Verma, Ritu [Department of Gastroenterology, Philadelphia, PA (United States); Pawel, Bruce [Department of Pathology, Philadelphia, PA (United States)

    2010-08-15

    Lipoprotein lipase deficiency (LLD) is a rare metabolic disorder that typically presents with skin xanthomas and pancreatitis in childhood. We report a case of LLD in an infant who presented with jaundice caused by a pancreatic head mass. Abdominal imaging also incidentally revealed hyperechoic renal masses caused by renal xanthomas. This appearance of the multiple abdominal masses makes this a unique infantile presentation of LLD. (orig.)

  11. Immune Response to Lipoproteins in Atherosclerosis

    OpenAIRE

    Sonia Samson; Lakshmi Mundkur; Kakkar, Vijay V

    2012-01-01

    Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation re...

  12. Immune Response to Lipoproteins in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sonia Samson

    2012-01-01

    Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  13. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Shore, V. (Lawrence Livermore Lab., CA); Salen, G.; Cheng, F.W.; Forte, T.; Shefer, S.; Tint, G.S.

    1981-11-01

    The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +/- 3.2 mg/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl esters are low, free cholesterol and phospholipids essentially normal, and triglycerides increased. The ratio of apoprotein (apo) to total cholesterol in the HDL of CTX was two to three times greater than normal. In the CTX HDL, the ratio of apoAI to apoAII was high, the proportion of apoC low, and a normally minor form of apoAI increased relative to other forms. The HDL in electron micrographs appeared normal morphologically and in particle size. The adnormalities in lipoprotein distribution profiles and composition of the plasma HDL result from metabolic defects that are not understood but may be linked to the genetic defect in bile acid synthesis in CTX. As a consequence, it is probable that the normal functions of the HDL, possibly including modulation of LDL-cholesterol uptake and the removal of excess cholesterol from peripheral tissues, are perturbed significantly in this disease.

  14. Characteristics of Lipoprotein Peak x Eluted from a Column with the Eluent of High-magnesium Ion Concentration in Lipoprotein Analysis Using the Cation-exchange Chromatography

    OpenAIRE

    Yuji Hirowatari; Hiroshi Yoshida; Yutaka Ogura; Hidekastu Yanai; Hideo Kurosawa; Norio Tada

    2005-01-01

    The new lipoprotein analysis method using a cation-exchange chromatography, which contains a sulfopropyl-ligand column and two magnesium ion-containing eluents was previously reported. This method can separate serum lipoproteins on the column gel with a magnesium ion concentration gradient and high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and an unspecified lipoprotein peak are eluted in order from the column. We have now characterize...

  15. Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes

    Directory of Open Access Journals (Sweden)

    Slatko Barton E

    2010-10-01

    Full Text Available Abstract Background Lymphatic filariasis and onchocerciasis are debilitating diseases caused by filarial nematodes. Disease pathogenesis is induced by inflammatory responses following the death of the parasite. Wolbachia endosymbionts of filariae are potent inducers of innate and adaptive inflammation and bacterial lipoproteins have been identified as the ligands that bind toll-like receptors (TLR 2 and TLR6. Lipoproteins are important structural and functional components of bacteria and therefore enzymes involved in Wolbachia lipoprotein biosynthesis are potential chemotherapeutic targets. Results Globomycin, a signal peptidase II (LspA inhibitor, has activity against Gram-negative bacteria and a putative lspA gene has been identified from the Wolbachia genome of Brugia malayi (wBm. The amino acids required for function are strictly conserved and functionality was verified by complementation tests in a temperature-sensitive Escherichia coli lspA mutant. Also, transformation of wild type E. coli with Wolbachia lspA conferred significant globomycin resistance. A cell-based screen has been developed utilizing a Wolbachia-containing Aedes albopictus cell line to assay novel compounds active against Wolbachia. Globomycin was screened using this assay, which resulted in a dose-dependent reduction in Wolbachia load. Furthermore, globomycin was also effective in reducing the motility and viability of adult B. malayi in vitro. Conclusions These studies validate lipoprotein biosynthesis as a target in an organism for which no genetic tools are available. Further studies to evaluate drugs targeting this pathway are underway as part of the A-WOL drug discovery and development program.

  16. MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

    Science.gov (United States)

    Wiesner, Philipp; Tafelmeier, Maria; Chittka, Dominik; Choi, Soo-Ho; Zhang, Li; Byun, Young Sup; Almazan, Felicidad; Yang, Xiaohong; Iqbal, Navaid; Chowdhury, Punam; Maisel, Alan; Witztum, Joseph L.; Handel, Tracy M.; Tsimikas, Sotirios; Miller, Yury I.

    2013-01-01

    Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis. PMID:23667177

  17. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  18. Connexin mutants and cataracts

    Directory of Open Access Journals (Sweden)

    Eric C Beyer

    2013-04-01

    Full Text Available The lens is a multicellular, but avascular tissue that must stay transparent to allow normal transmission of light and focusing of it on the retina. Damage to lens cells and/or proteins can cause cataracts, opacities that disrupt these processes. The normal survival of the lens is facilitated by an extensive network of gap junctions formed predominantly of connexin46 and connexin50. Mutations of the genes that encode these connexins (GJA3 and GJA8 have been identified and linked to inheritance of cataracts in human families and mouse lines. In vitro expression studies of several of these mutants have shown that they exhibit abnormalities that may lead to disease. Many of the mutants reduce or modify intercellular communication due to channel alterations (including loss of function or altered gating or due to impaired cellular trafficking which reduces the number of gap junction channels within the plasma membrane. However, the abnormalities detected in studies of other mutants suggest that they cause cataracts through other mechanisms including gain of hemichannel function (leading to cell injury and death and formation of cytoplasmic accumulations (that may act as light scattering particles. These observations and the anticipated results of ongoing studies should elucidate the mechanisms of cataract development due to mutations of lens connexins and abnormalities of other lens proteins. They may also contribute to our understanding of the mechanisms of disease due to connexin mutations in other tissues.

  19. Fish plasma lipoproteins--comparative observations in serranides and sparides.

    Science.gov (United States)

    Santulli, A; Cusenza, L; Modica, A; Curatolo, A; D'Amelio, V

    1991-01-01

    1. Diet, time from last feeding, temperature, season and sexual stage are some of the factors influencing the lipoprotein pattern. 2. Keeping these factors constant species-specific differences observed among lipoprotein patterns of Sparus aurata, Puntazzo puntazzo, Diplodus sargus, Diplodus vulgaris and Dicentrarchus labrax are discussed. 3. Feeding habits and therefore lipid absorption and the rate of lipoprotein maturation process are the factors determining the observed differences.

  20. Increased transvascular low density lipoprotein transport in insulin dependent diabetes

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo

    2003-01-01

    BACKGROUND: The increased risk of atherosclerosis associated with diabetes cannot be explained by conventional cardiovascular risk factors alone. We hypothesized that transvascular lipoprotein transport may be increased in patients with diabetes, possibly explaining increased intimal lipoprotein ...... be increased in patients with type 1 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with type 1 diabetes, possibly explaining accelerated development of atherosclerosis....

  1. Computational lipidology: predicting lipoprotein density profiles in human blood plasma.

    Directory of Open Access Journals (Sweden)

    Katrin Hübner

    2008-05-01

    Full Text Available Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond "bad" and "good" cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL, we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile is calculated. As our main results, we (i successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS, revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia.

  2. Outer membrane lipoprotein biogenesis: Lol is not the end.

    Science.gov (United States)

    Konovalova, Anna; Silhavy, Thomas J

    2015-10-05

    Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology.

  3. Lipoprotein glomerulopathy treated with LDL-apheresis (Heparin-induced Extracorporeal Lipoprotein Precipitation system: a case report

    Directory of Open Access Journals (Sweden)

    Rivasi Paolo

    2009-12-01

    Full Text Available Abstract Introduction Lipoprotein glomerulopathy is a glomerulonephritis which was described for the first time by Saito in 1989 and is currently acknowledged as a separate nosological entity. It is histologically characterized by a marked dilatation of the glomerular capillaries and the presence of lipoprotein thrombi in the glomerular lumens. The dyslipidemic profile is similar to that of type III dyslipoproteinemia with Apolipoprotein E values that are often high; proteinuria and renal dysfunction are present. Proteinuria often does not respond to steroid and cytostatic treatments. The phenotypic expression of lipoprotein glomerulopathy is most probably correlated to a genetic alteration of the lipoprotein metabolism (mutation of the Apolipoprotein E coding gene. In literature, lipoprotein glomerulopathies have mainly been reported in Japanese and Chinese subjects, except for three cases in the Caucasian race, reported in France and the USA. Case presentation We describe the case of a 60-year-old female, Caucasian patient suffering from lipoprotein glomerulopathy, carrier of a new mutation on the Apolipoprotein E gene (Apolipoprotein EMODENA, and treated successfully with low density lipoprotein-apheresis with the Heparin induced extracorporeal lipoprotein precipitation system. After a first phase of therapeutic protocol with statins, the patient was admitted for nephrotic syndrome, renal failure and hypertension. Since conventional treatment alone was not able to control dyslipidemia, aphaeretic treatment with heparin-induced Extracorporeal Lipoprotein Precipitation - apheresis (HELP-apheresis was started to maintain angiotensin converting enzyme inhibitor therapy for the treatment of hypertension. Treatment with HELP-apheresis led to a complete remission of the proteinuria in a very short time (four months, as well as control of hypercholesterolemia and renal function recovery. Conclusion According to this case of lipoprotein glomerulopathy

  4. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  5. Turkish Heart Study: lipids, lipoproteins, and apolipoproteins.

    Science.gov (United States)

    Mahley, R W; Palaoğlu, K E; Atak, Z; Dawson-Pepin, J; Langlois, A M; Cheung, V; Onat, H; Fulks, P; Mahley, L L; Vakar, F

    1995-04-01

    We examined the plasma lipids, lipoproteins, and selected apolipoproteins in approximately 9,000 men and women from six different regions of Turkey with markedly different diets, ranging from an Aegean coast diet high in olive oil (plasma cholesteryl ester fatty acids enriched in monounsaturated fatty acids) to an inland Anatolian diet high in meat and dairy products (plasma cholesteryl esters enriched in saturated fatty acids). The rural population consuming an olive oil-rich diet had the lowest plasma cholesterol levels (men, 149 mg/dl; women, 150 mg/dl). The urban populations of Istanbul and Adana had higher plasma cholesterol levels (men, 202 and 184 mg/dl, respectively; women, 181 and 190 mg/dl, respectively). Affluent men had the highest cholesterol levels (207 mg/dl). The low density lipoprotein (LDL) cholesterol levels tended to parallel the total cholesterol levels (highest for Istanbul men at 136 mg/dl and lowest for Aegean coast men and women at approximately 100 mg/dl). Strikingly, the Turkish people were found to have very low levels of high density lipoprotein (HDL) cholesterol (HDL-C) (mean values for all six regions: men, 34-38 mg/dl; women, 37-45 mg/dl) and total cholesterol/HDL-C ratios that were high (mean values for all six regions: men, 4.5-5.5; women, 3.9-5.0). The low HDL-C levels appear to be caused, at least in part, by a genetic factor. Triglyceride levels also tended to be high in Turkish men (approximately 120-150 mg/dl) and women (approximately 90-110 mg/dl). Thus, even though the total plasma cholesterol levels are not excessively elevated in comparison to those in other populations, the presence of low HDL-C or low HDL-C coupled with mildly elevated triglyceride levels may represent a significant risk factor for heart disease in the Turkish population. Affluence and higher education were associated with higher cholesterol levels. Lack of physical activity, smoking, and alcohol consumption also tended to be associated with a

  6. Mendelian Disorders of High-Density Lipoprotein Metabolism

    NARCIS (Netherlands)

    Oldoni, Federico; Sinke, Richard J.; Kuivenhoven, Jan Albert

    2014-01-01

    High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL chol

  7. Prediction of lipoprotein signal peptides in Gram-negative bacteria

    DEFF Research Database (Denmark)

    Juncker, Agnieszka; Willenbrock, Hanni; Von Heijne, G.

    2003-01-01

    A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor...

  8. TRIIODOTHYRONINE RAPIDLY LOWERS PLASMA-LIPOPROTEIN (A) IN HYPOTHYROID SUBJECTS

    NARCIS (Netherlands)

    DULLAART, RPF; VANDOORMAAL, JJ; HOOGENBERG, K; SLUITER, WJ

    1995-01-01

    Background: Increases in plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) are well known in primary hypothyroidism, but it is uncertain whether thyroid dysfunction is associated with elevated levels of the atherogenic lipoprotein (a) (Lp(a)). Methods: The effect of short

  9. A clustering analysis of lipoprotein diameters in the metabolic syndrome

    Science.gov (United States)

    The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

  10. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention.

    Science.gov (United States)

    Millán, Jesús; Pintó, Xavier; Muñoz, Anna; Zúñiga, Manuel; Rubiés-Prat, Joan; Pallardo, Luis Felipe; Masana, Luis; Mangas, Alipio; Hernández-Mijares, Antonio; González-Santos, Pedro; Ascaso, Juan F; Pedro-Botet, Juan

    2009-01-01

    Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or "atherogenic indices" have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol.

  11. Modulation of low-density lipoprotein-induced inhibition of intercellular communication by antioxidants and high-density lipoproteins

    NARCIS (Netherlands)

    Zwijsen, R M; de Haan, L. H. J.; Kuivenhoven, J A; Nusselder, I C

    1991-01-01

    In order to study the capacity of antioxidants and high-density lipoproteins (HDL) to modulate the effects of low-density lipoprotein (LDL) on intercellular communication, arterial smooth muscle cells and a dye transfer method were used. LDL, in contrast to HDL, inhibited the communication between a

  12. A fibrinogen-binding lipoprotein contributes to the virulence of Haemophilus ducreyi in humans.

    Science.gov (United States)

    Bauer, Margaret E; Townsend, Carisa A; Doster, Ryan S; Fortney, Kate R; Zwickl, Beth W; Katz, Barry P; Spinola, Stanley M; Janowicz, Diane M

    2009-03-01

    A gene expression study of Haemophilus ducreyi identified the hypothetical lipoprotein HD0192, renamed here "fibrinogen binder A" (FgbA), as being preferentially expressed in vivo. To test the role played by fgbA in virulence, an isogenic fgbA mutant (35000HPfgbA) was constructed using H. ducreyi 35000HP, and 6 volunteers were experimentally infected with 35000HP or 35000HPfgbA. The overall pustule-formation rate was 61.1% at parent sites and 22.2% at mutant sites (P = .019). Papules were significantly smaller at mutant sites than at parent sites (13.3 vs. 37.9 mm(2); P = .002) 24 h after inoculation. Thus, fgbA contributed significantly to the virulence of H. ducreyi in humans. In vitro experiments demonstrated that fgbA encodes a fibrinogen-binding protein; no other fibrinogen-binding proteins were identified in 35000HP. fgbA was conserved among clinical isolates of both class I and II H. ducreyi strains, supporting the finding that fgbA is important for H. ducreyi infection.

  13. Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

    DEFF Research Database (Denmark)

    Ollila, O. H. S.; Lamberg, A.; Lehtivaara, M.

    2012-01-01

    Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentia...... of interfacial tension becomes significant for particles with a radius of similar to 5 nm, when the area per molecule in the surface region is...

  14. Apoc2 loss-of-function zebrafish mutant as a genetic model of hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Chao Liu

    2015-08-01

    Full Text Available Apolipoprotein C-II (APOC2 is an obligatory activator of lipoprotein lipase. Human patients with APOC2 deficiency display severe hypertriglyceridemia while consuming a normal diet, often manifesting xanthomas, lipemia retinalis and pancreatitis. Hypertriglyceridemia is also an important risk factor for development of cardiovascular disease. Animal models to study hypertriglyceridemia are limited, with no Apoc2-knockout mouse reported. To develop a genetic model of hypertriglyceridemia, we generated an apoc2 mutant zebrafish characterized by the loss of Apoc2 function. apoc2 mutants show decreased plasma lipase activity and display chylomicronemia and severe hypertriglyceridemia, which closely resemble the phenotype observed in human patients with APOC2 deficiency. The hypertriglyceridemia in apoc2 mutants is rescued by injection of plasma from wild-type zebrafish or by injection of a human APOC2 mimetic peptide. Consistent with a previous report of a transient apoc2 knockdown, apoc2 mutant larvae have a minor delay in yolk consumption and angiogenesis. Furthermore, apoc2 mutants fed a normal diet accumulate lipid and lipid-laden macrophages in the vasculature, which resemble early events in the development of human atherosclerotic lesions. In addition, apoc2 mutant embryos show ectopic overgrowth of pancreas. Taken together, our data suggest that the apoc2 mutant zebrafish is a robust and versatile animal model to study hypertriglyceridemia and the mechanisms involved in the pathogenesis of associated human diseases.

  15. An efficient depyrogenation method for recombinant bacterial outer membrane lipoproteins.

    Science.gov (United States)

    Basto, Afonso P; Morais, Joana; Marcelino, Eduardo; Leitão, Alexandre; Santos, Dulce M

    2014-06-01

    Bacterial outer membrane lipoproteins are anchored in the outer membrane lipid layer in close association with lipopolysaccharides (LPS) and with other hydrophobic membrane proteins, making their purification technically challenging. We have previously shown that a thorough delipidation of outer membrane preparations from the Escherichia coli expression host is an important step to eliminate contaminant proteins when purifying recombinant antigens expressed in fusion with the Pseudomonas aeruginosa OprI lipoprotein. Here we report the cloning and expression of three antigens in fusion with OprI (ovalbumin, eGFP and BbPDI) and our efforts to deal with the variable LPS contamination levels observed in different batches of purified lipoproteins. The use of polymyxin B columns or endotoxin removal polycationic magnetic beads for depyrogenation of purified lipoproteins resulted in high protein losses and the use of Triton X-114 or sodium deoxycholate during the course of affinity chromatography showed to be ineffective to reduce LPS contamination. Instead, performing a hot phenol/water LPS extraction from outer membrane preparations prior to metal affinity chromatography allowed the purification of the recombinant fusion lipoproteins with LPS contents below 0.02EU/μg of protein. The purified recombinant lipoproteins retain their capacity to stimulate bone marrow-derived dendritic cells allowing for the study of their immunomodulatory properties through TLR2/1. This is a simple and easy to scale up method that can also be considered for the purification of other outer membrane lipoproteins.

  16. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

    LENUS (Irish Health Repository)

    Harrison, Michael

    2012-06-06

    AbstractBackgroundMany of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects.MethodsUsing a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL).ResultsThe intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state.ConclusionsThese findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

  17. Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

    Directory of Open Access Journals (Sweden)

    Harrison Michael

    2012-07-01

    Full Text Available Abstract Background Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS, it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. Methods Using a randomized cross-over design, very low density lipoprotein (VLDL responses were evaluated in eight men on the morning after i an inactive control trial (CON, ii exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF, and iii after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL. Results The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium particle range. VLDL-TG in smaller particles (29–43 nm was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. Conclusions These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in

  18. Staphylococcus aureus Lpl Lipoproteins Delay G2/M Phase Transition in HeLa Cells

    Science.gov (United States)

    Nguyen, Minh-Thu; Deplanche, Martine; Nega, Mulugeta; Le Loir, Yves; Peisl, Loulou; Götz, Friedrich; Berkova, Nadia

    2016-01-01

    The cell cycle is an ordered set of events, leading to cell growth and division into two daughter cells. The eukaryotic cell cycle consists of interphase (G1, S, and G2 phases), followed by the mitotic phase and G0 phase. Many bacterial pathogens secrete cyclomodulins that interfere with the host cell cycle. In Staphylococcus aureus four cyclomodulins have been described so far that all represent toxins and are secreted into the culture supernatant. Here we show that the membrane-anchored lipoprotein-like proteins (Lpl), encoded on a genomic island called νSaα, interact with the cell cycle of HeLa cells. By comparing wild type and lpl deletion mutant it turned out that the lpl cluster is causative for the G2/M phase transition delay and also contributes to increased invasion frequency. The lipoprotein Lpl1, a representative of the lpl cluster, also caused G2/M phase transition delay. Interestingly, the lipid modification, which is essential for TLR2 signaling and activation of the immune system, is not necessary for cyclomodulin activity. Unlike the other staphylococcal cyclomodulins Lpl1 shows no cytotoxicity even at high concentrations. As all Lpl proteins are highly conserved there might be a common function that is accentuated by their multiplicity in a tandem gene cluster. The cell surface localized Lpls' suggests a correlation between G2/M phase transition delay and host cell invasion. PMID:28083519

  19. The influence of lipoprotein(a) on fibrinolytic activity

    OpenAIRE

    Rahajuningsih D. Setiabudy; Marzuki Suryaatmadja; Fifi Henrika

    2004-01-01

    Lipoprotein(a) is a plasma lipoprotein whose structure and composition are similar with low density lipoprotein (LDL) with an addition of apo(a) that is bound to apo B100. The structure of apo(a) is similar with plasminogen, a proenzym in fibrinolytic system. Due to this similarity, it is assumed that Lp(a) can inhibit plasminogen activity and decreases fibrinolytic activity. The purpose of this study is to prove that addition of Lp(a) to normal plasma can inhibit fibrinolytic activity. Four ...

  20. Nanobiotechnology applications of reconstituted high density lipoprotein.

    Science.gov (United States)

    Ryan, Robert O

    2010-12-01

    High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions.

  1. Lipoprotein(a in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Michele Malaguarnera

    2013-01-01

    Full Text Available Lipoprotein(a (Lp(a is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100 particle attached by a disulphide bridge to apo(a. Many observations have pointed out that Lp(a levels may be a risk factor for cardiovascular diseases. Lp(a inhibits the activation of transforming growth factor (TGF and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a-lowering therapy might be beneficial in patients with high Lp(a levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.

  2. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  3. Modulation of lipoprotein receptor functions by intracellular adaptor proteins.

    Science.gov (United States)

    Stolt, Peggy C; Bock, Hans H

    2006-10-01

    Members of the low density lipoprotein (LDL) receptor gene family are critically involved in a wide range of physiological processes including lipid and vitamin homeostasis, cellular migration, neurodevelopment, and synaptic plasticity, to name a few. Lipoprotein receptors exert these diverse biological functions by acting as cellular uptake receptors or by inducing intracellular signaling cascades. It was discovered that a short sequence in the intracellular region of all lipoprotein receptors, Asn-Pro-X-Tyr (NPXY) is important for mediating either endocytosis or signal transduction events, and that this motif serves as a binding site for phosphotyrosine-binding (PTB) domain containing scaffold proteins. These molecular adaptors connect the transmembrane receptors with the endocytosis machinery and regulate cellular trafficking, or function as assembly sites for dynamic multi-protein signaling complexes. Whereas the LDL receptor represents the archetype of an endocytic lipoprotein receptor, the structurally closely related apolipoprotein E receptor 2 (apoER2) and very low density lipoprotein (VLDL) receptor activate a kinase-dependent intracellular signaling cascade after binding to the neuronal signaling molecule Reelin. This review focuses on two related PTB domain containing adaptor proteins that mediate these divergent lipoprotein receptor responses, ARH (autosomal recessive hypercholesterolemia protein) and Dab1 (disabled-1), and discusses the structural and molecular basis of this different behaviour.

  4. The use of transgenic animals to study lipoprotein metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, E.M.; Plump, A.S.

    1993-12-01

    The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

  5. Mechanisms and signiifcance of lipoprotein(a) in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Ning Xu; Xue-Guang Zhang

    2009-01-01

    BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid proifles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords "hepatocellular carcinoma" and "lipoprotein(a)". The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apo-lipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolismin vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein(a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display signiifcant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.

  6. Dissecting the proteome of lipoproteins: New biomarkers for cardiovascular diseases?

    Directory of Open Access Journals (Sweden)

    Anne von Zychlinski

    2015-06-01

    Full Text Available Proteomics has proven to be a powerful tool for the characterization of lipoproteins and has provided important insights into the biochemistry and pathophysiology of various lipoprotein classes. It has significantly contributed to the way we now see lipoproteins as complex particles not only involved in lipid transport and exchange, but also in processes such as immune response, inflammation and wound healing. Ongoing proteomics research is focussing on the identification of new candidate markers for cardiovascular disease, the leading cause of death worldwide. The ratio between good cholesterol (high density lipoprotein and bad cholesterol (low density lipoprotein is routinely used to estimate an individual’s risk for developing premature coronary heart disease. While statin therapy has proven effects in reducing cardiovascular events, other therapies such as resins, fibrates and niacin have failed to substantially reduce cardiovascular risk. Thus new targets and candidate biomarkers for risk assessment and for the development of alternative drugs and treatments of disease are needed. Here we review the recent findings in lipoprotein proteomics with the main emphasis on studies that differentially displayed various states of diseases and on new targeted, high throughput strategies with the capability to translate discovery findings into the clinical context of large cohort analyzes.

  7. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.

    Science.gov (United States)

    Neufert, C; Pai, R K; Noss, E H; Berger, M; Boom, W H; Harding, C V

    2001-08-01

    Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

  8. SAA is Found on ApoB-Containing Lipoproteins in Obese Diabetic Humans

    OpenAIRE

    Jahangiri, Anisa; Wilson, Patricia G.; Hou, Tianfei; Brown, Aparna; King, Victoria L.; Tannock, Lisa R.

    2013-01-01

    In murine models of obesity/diabetes there is an increase in plasma SAA levels along with redistribution of SAA from high density lipoprotein (HDL) to apo-B containing lipoprotein particles, namely low density lipoprotein (LDL) and very low density lipoprotein (VLDL). The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n=14), metabolic ...

  9. Lipid droplet pattern and nondroplet-like structure in two fat mutants of Caenorhabditis elegans revealed by coherent anti-Stokes Raman scattering microscopy

    Science.gov (United States)

    Yi, Yung-Hsiang; Chien, Cheng-Hao; Chen, Wei-Wen; Ma, Tian-Hsiang; Liu, Kuan-Yu; Chang, Yu-Sun; Chang, Ta-Chau; Lo, Szecheng J.

    2014-01-01

    Lipid is an important energy source and essential component for plasma and organelle membranes in all kinds of cells. Coherent anti-Stokes Raman scattering (CARS) microscopy is a label-free and nonlinear optical technique that can be used to monitor the lipid distribution in live organisms. Here, we utilize CARS microscopy to investigate the pattern of lipid droplets in two live Caenorhabditis elegans mutants (fat-2 and fat-3). The CARS images showed a striking decrease in the size, number, and content of lipid droplets in the fat-2 mutant but a slight difference in the fat-3 mutant as compared with the wild-type worm. Moreover, a nondroplet-like structure with enhanced CARS signal was detected for the first time in the uterus of fat-2 and fat-3 mutants. In addition, transgenic fat-2 mutant expressing a GFP fusion protein of vitellogenin-2 (a yolk lipoprotein) revealed that the enhanced CARS signal colocalized with the GFP signal, which suggests that the nondroplet-like structure is primarily due to the accumulation of yolk lipoproteins. Together, this study implies that CARS microscopy is a potential tool to study the distribution of yolk lipoproteins, in addition to lipid droplets, in live animals.

  10. Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process.

    Science.gov (United States)

    Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto

    2014-01-01

    Discoidal high-density lipoproteins (D-HDL) are critical intermediates in reverse cholesterol transport. Most of the present knowledge of D-HDL is based on studies with reconstituted lipoprotein complexes of apolipoprotein A-I (apoA-I) obtained by cholate dialysis (CD). D-HDL can also be generated by the direct microsolubilization (DM) of phospholipid vesicles at the gel/fluid phase transition temperature, a process mechanistically similar to the "in vivo" apoAI lipidation via ABCA1. We compared the apoA-I configuration in D-HDL reconstituted with dimyristoylphosphatidylcholine by both procedures using fluorescence resonance energy transfer measurements with apoA-I tryptophan mutants and fluorescently labeled cysteine mutants. Results indicate that apoA-I configuration in D-HDL depends on the reconstitution process and are consistent with a "double belt" molecular arrangement with different helix registry. As reported by others, a configuration with juxtaposition of helices 5 of each apoAI monomer (5/5 registry) predominates in D-HDL obtained by CD. However, a configuration with helix 5 of one monomer juxtaposed with helix 2 of the other (5/2 registry) would predominate in D-HDL generated by DM. Moreover, we also show that the kinetics of cholesterol efflux from macrophage cultures depends on the reconstitution process, suggesting that apoAI configuration is important for this HDL function.

  11. Interpretation of Dieter Rams Design Philosophy from Braun Products%从博朗产品诠释迪特尔·拉姆斯的设计哲学

    Institute of Scientific and Technical Information of China (English)

    陈岩

    2012-01-01

    According to Dieter Abrams lifetime design method as the research object, it discussed his design philosophy, from Braun electrical products design as the main line, elaborated the product design simple, delicate, perfect and noble, analyzed the design philosophy of how to integrate the rams in Braun products, products and how to serve for the life, for the public service, and served for the function requirements. The rams design created excellent Braun electrical and excellent managementsystem, on this foundation, put forward the design thought of Abrams affect apple and other modem product design application.%以迪特尔·拉姆斯一生的设计方法为研究对象,阐述了他的设计哲学思想,以博朗电器产品的造型设计为主,论述了产品设计的简约、细致、完美与高贵,分析拉姆斯的设计哲学如何融入在博朗的产品中,提出产品又是如何为生活、大众、功能服务的要求。通过拉姆斯的设计思想塑造出优秀的博朗电器以及出色的管理制度,在此基础上,拉姆斯的设计思想又如何影响到苹果等现代产品设计的应用。

  12. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J., E-mail: rbrown@mun.ca

    2014-09-05

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  13. Pistachio intake increases high density lipoprotein levels and inhibits low-density lipoprotein oxidation in rats.

    Science.gov (United States)

    Aksoy, Nur; Aksoy, Mehmet; Bagci, Cahit; Gergerlioglu, H Serdar; Celik, Hakim; Herken, Emine; Yaman, Abdullah; Tarakcioglu, Mehmet; Soydinc, Serdar; Sari, Ibrahim; Davutoglu, Vedat

    2007-05-01

    There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pistachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n=12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.

  14. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase.

    Science.gov (United States)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M; Brown, Robert J

    2014-09-05

    Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  15. Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism

    NARCIS (Netherlands)

    Dashty Rahmatabady, Monireh; Motazacker, Mohammad M.; Levels, Johannes; de Vries, Marcel; Mahmoudi, Morteza; Peppelenbosch, Maikel; Rezaee, Farhad

    2014-01-01

    Apart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis fr

  16. Aminoacylation of the N-terminal cysteine is essential for Lol-dependent release of lipoproteins from membranes but does not depend on lipoprotein sorting signals.

    Science.gov (United States)

    Fukuda, Ayumu; Matsuyama, Shin-Ichi; Hara, Takashi; Nakayama, Jiro; Nagasawa, Hiromichi; Tokuda, Hajime

    2002-11-08

    Lipoproteins are present in a wide variety of bacteria and are anchored to membranes through lipids attached to the N-terminal cysteine. The Lol system of Escherichia coli mediates the membrane-specific localization of lipoproteins. Aspartate at position 2 functions as a Lol avoidance signal and causes the retention of lipoproteins in the inner membrane, whereas lipoproteins having residues other than aspartate at position 2 are released from the inner membrane and localized to the outer membrane by the Lol system. Phospholipid:apolipoprotein transacylase, Lnt, catalyzes the last step of lipoprotein modification, converting apolipoprotein into mature lipoprotein. To reveal the importance of this aminoacylation for the Lol-dependent membrane localization, apolipoproteins were prepared by inhibiting lipoprotein maturation. Lnt was also purified and used to convert apolipoprotein into mature lipoprotein in vitro. The release of these lipoproteins was examined in proteoliposomes. We show here that the aminoacylation is essential for the Lol-dependent release of lipoproteins from membranes. Furthermore, lipoproteins with aspartate at position 2 were found to be aminoacylated both in vivo and in vitro, indicating that the lipoprotein-sorting signal does not affect lipid modification.

  17. The NlpD lipoprotein is a novel Yersinia pestis virulence factor essential for the development of plague.

    Directory of Open Access Journals (Sweden)

    Avital Tidhar

    Full Text Available Yersinia pestis is the causative agent of plague. Previously we have isolated an attenuated Y. pestis transposon insertion mutant in which the pcm gene was disrupted. In the present study, we investigated the expression and the role of pcm locus genes in Y. pestis pathogenesis using a set of isogenic surE, pcm, nlpD and rpoS mutants of the fully virulent Kimberley53 strain. We show that in Y. pestis, nlpD expression is controlled from elements residing within the upstream genes surE and pcm. The NlpD lipoprotein is the only factor encoded from the pcm locus that is essential for Y. pestis virulence. A chromosomal deletion of the nlpD gene sequence resulted in a drastic reduction in virulence to an LD(50 of at least 10(7 cfu for subcutaneous and airway routes of infection. The mutant was unable to colonize mouse organs following infection. The filamented morphology of the nlpD mutant indicates that NlpD is involved in cell separation; however, deletion of nlpD did not affect in vitro growth rate. Trans-complementation experiments with the Y. pestis nlpD gene restored virulence and all other phenotypic defects. Finally, we demonstrated that subcutaneous administration of the nlpD mutant could protect animals against bubonic and primary pneumonic plague. Taken together, these results demonstrate that Y. pestis NlpD is a novel virulence factor essential for the development of bubonic and pneumonic plague. Further, the nlpD mutant is superior to the EV76 prototype live vaccine strain in immunogenicity and in conferring effective protective immunity. Thus it could serve as a basis for a very potent live vaccine against bubonic and pneumonic plague.

  18. Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data.

    Directory of Open Access Journals (Sweden)

    Simon C Mathews

    Full Text Available BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C ≥ 40; TG<150; and TG/HDL-C<3. METHODS: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10(-6. The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150 was also effective (F = 42.8, p<10(-5. However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150 was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10(-5 with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively. LDL density phenotype neared significance (F = 2.85, p = 0.094 and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47 alone or add discriminatory power to ATP-III targets. CONCLUSIONS: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical

  19. New and emerging regulators of intestinal lipoprotein secretion.

    Science.gov (United States)

    Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Lewis, Gary F

    2014-04-01

    Overproduction of hepatic apoB100-containing VLDL particles has been well documented in animal models and in humans with insulin resistance such as the metabolic syndrome and type 2 diabetes, and contributes to the typical dyslipidemia of these conditions. In addition, postprandial hyperlipidemia and elevated plasma concentrations of intestinal apoB48-containing chylomicron and chylomicron remnant particles have been demonstrated in insulin resistant states. Intestinal lipoprotein production is primarily determined by the amount of fat ingested and absorbed. Until approximately 10 years ago, however, relatively little attention was paid to the role of the intestine itself in regulating the production of triglyceride-rich lipoproteins (TRL) and its dysregulation in pathological states such as insulin resistance. We and others have shown that insulin resistant animal models and humans are characterized by overproduction of intestinal apoB48-containing lipoproteins. Whereas various factors are known to regulate hepatic lipoprotein particle production, less is known about factors that regulate the production of intestinal lipoprotein particles. Monosacharides, plasma free fatty acids (FFA), resveratrol, intestinal peptides (e.g. GLP-1 and GLP-2), and pancreatic hormones (e.g. insulin) have recently been shown to be important regulators of intestinal lipoprotein secretion. Available evidence in humans and animal models strongly supports the concept that the small intestine is not merely an absorptive organ but rather plays an active role in regulating the rate of production of chylomicrons in fed and fasting states. Metabolic signals in insulin resistance and type 2 diabetes and in some cases an aberrant intestinal response to these factors contribute to the enhanced formation and secretion of TRL. Understanding the regulation of intestinal lipoprotein production is imperative for the development of new therapeutic strategies for the prevention and treatment of

  20. Hydrolysis of guinea pig nascent very low density lipoproteins catalyzed by lipoprotein lipase: activation by hjman apolipoprotein C-II.

    Science.gov (United States)

    Fitzharris, T J; Quinn, D M; Goh, E H; Johnson, J D; Kashyap, M L; Srivastava, L S; Jackson, R L; Harmony, J A

    1981-08-01

    Very low density lipoproteins isolated from guinea pig liver perfusate (VLDLp) lack the equivalent of human apolipoprotein C-II (apoC-II), the activator of lipoprotein lipase (LpL). These lipoproteins are therefore ideal substrates with which to investigate the mechanism by which apoC-II activates the enzyme. VLDLp binds apoC-II, and apoC-II associated with VLDLp markedly increases the rate of lipoprotein lipase-catalyzed hydrolysis of VLDLp-triglycerides. The activator potency of apoC-II is independent of the method of enrichment of VLDLp with apoC-II: delipidated human apoC-II and apoC-II transferred from human high density lipoproteins activate lipoprotein lipase to equal extents. ApoC-II causes pH-dependent changes in both apparent Km and VmaX of LpL-catalyzed hydrolysis of VLDLp-triglycerides. At pH l7.4--7.5, the major effects of apoC-II is to decrease the apparent Km by 3.3--4.0 fold. The apparent Vmax is increased 1.3-fold. At pH 6.5 and 8.5, the decrease of apparent Km is less marked, 1.6-fold and 1.4-fold, respectively. At pH 6.5, apoC-II increases the apparent Vmax ty 1.3-fold, while at pH 8.5 the primary effect of apoC-II is a 1.6-fold increase of apparent Vmax. Based on a simple kinetic model, the data suggest that apoC-II favors direct interaction between enzyme and triglyceride within the lipoprotein particle, as well as subsequent catalytic turnover.

  1. Gutscheine und Protektionismus / Gerald Braun

    Index Scriptorium Estoniae

    Braun, Gerald

    2016-01-01

    Euroopa Kohtu otsusest, mis käsitleb küsimust, millistel tingimustel võivad tööandjad väljastada oma töötajatele maksusoodustusega talonge, mida saab kasutada majutuseks, meelelahutuseks ja/või toitlustuseks (C‑179/14). Vt. ka lk. 439-440

  2. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-09-15

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature's method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL-drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

  3. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N. K.

    2013-10-01

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  4. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar, E-mail: neelesh81mph@gmail.com; Jain, N. K., E-mail: dr.jnarendr@gmail.com [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-10-15

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  5. Influence of liver cancer on lipid and lipoprotein metabolism

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2006-03-01

    Full Text Available Abstract Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL. Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG, cholesterol, free fatty acids (FFA, HDL, low-density lipoproteins (LDL, lipoprotein (a (Lp(a, apolipoprotein AI (apoAI and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents.

  6. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G

    2016-01-01

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need.......1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate...

  7. Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice

    Indian Academy of Sciences (India)

    HAILONG OU; QINGHAI ZHANG; JIA ZENG

    2016-06-01

    The defect of low density lipoprotein receptor disturbs cholesterol metabolism and causes familial hypercholesterolaemia(FH). In this study, we directly delivered exogenousLdlrgene into the liver of FH model mice (Ldlr − / −) by lentiviral genetransfer system. The results showed that theLdlrgene controlled by hepatocyte-specific human thyroxine-binding globulin(TBG) promoter successfully and exclusively expressed in livers. We found that, although, the content of high density lipopro-tein in serum was not significantly affected by theLdlrgene expression, the serum low density lipoprotein level was reducedby 46%, associated with a 30% and 28% decrease in triglyceride and total cholesterol, respectively, compared to uninjectedLdlr − / −mice. Moreover, the TBG directed expression ofLdlrsignificantly decreased the lipid accumulation in liver andreduced plaque burden in aorta (32%). Our results indicated that the hepatocyte-specific expression ofLdlrgene strikinglylowered serum lipid levels and resulted in amelioration of hypercholesterolaemia.

  8. Circulating lipoproteins are a crucial component of host defense against invasive Salmonella typhimurium infection.

    NARCIS (Netherlands)

    Netea, M.G.; Joosten, L.A.B.; Keuter, M.; Wagener, F.A.D.T.G.; Stalenhoef, A.F.H.; Meer, J.W.M. van der; Kullberg, B.J.

    2009-01-01

    BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS), thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/-) mice, with a 7-fold i

  9. Circulating Oxidized Low-Density Lipoproteins and Antibodies against Oxidized Low-Density Lipoproteins as Potential Biomarkers of Colorectal Cancer

    OpenAIRE

    2015-01-01

    Introduction. The aim of the study was evaluation of the diagnostic utility of serum oxidized low-density lipoproteins (oxLDL), antibodies against oxLDLs (o-LAB), and CEA as risk markers of colorectal cancer (CRC). Material and Methods. The serum levels of study factors were measured in 73 patients with CRC and in 35 healthy controls who were gender- and BMI-matched to the study group. Concentrations of oxLDL, o-LAB, and CEA were detected in ELISA tests. Serum lipids, lipoproteins, and gl...

  10. Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride-rich lipoproteins and lipolysis products.

    Science.gov (United States)

    Sasaki, A; Goldberg, I J

    1992-07-25

    Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was

  11. Wild Accessions and Mutant Resources

    DEFF Research Database (Denmark)

    Kawaguchi, Masayoshi; Sandal, Niels Nørgaard

    2014-01-01

    Lotus japonicus, Lotus burttii, and Lotus filicaulis are species of Lotus genus that are utilized for molecular genetic analysis such as the construction of a linkage map and QTL analysis. Among them, a number of mutants have been isolated from two wild accessions: L. japonicus Gifu B-129...

  12. Apolipoprotein B-containing lipoprotein particle assembly: Lipid capacity of the nascent lipoprotein particle

    Energy Technology Data Exchange (ETDEWEB)

    Manchekar, Medha; Forte, Trudy M.; Datta, Geeta; Richardson, Paul E.; Segrest, Jere P.; Dashti, Nassrin

    2003-12-01

    We previously proposed that the N-terminal 1000 residue {beta}{alpha}{sub 1} domain of apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey lipovitellin (LV). In support of this ''lipid pocket'' hypothesis, apoB:1000 (residues 1-1000) was shown to be secreted by a stable transformant of McA-RH7777 cells as a monodisperse particle with HDL{sub 3} density and Stokes diameter of 112 {angstrom}. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the sequence homologous to LV, was secreted as a particle considerably more dense than HDL with Stokes diameter of 110 {angstrom}. The purpose of the present study was to determine the stoichiometry of the lipid component of the apoB:931 and apoB:1000 particles. This was accomplished by metabolic labeling of cells with either [{sup 14}C]oleic acid or [{sup 3}H]glycerol followed by immunoprecipitation (IP) or nondenaturing gradient gel electrophoresis (NDGGE) of secreted lipoproteins and by immunoaffinity chromatography of secreted unlabeled lipoproteins. The [{sup 3}H]-labeled apoB:1000-containing particles, isolated by NDGGE, contained 50 phospholipids (PL) and 11 triacylglycerols (TAG) molecules per particle. In contrast, apoB:931-containing particles contained only a few molecules of PL and were devoid of TAG. The unlabeled apoB:1000-containing particles isolated by immunoaffinity chromatography and analyzed for lipid mass, contained 56 PL, 8 TAG, and 7 cholesteryl ester molecules per particle. The surface:core lipid ratio of apoB:1000-containing particles was approximately 4:1 and was not affected by incubation of cells with oleate. Although small amounts of microsomal triglyceride transfer protein (MTP) were associated with apoB:1000-containing particles, it never approached a 1:1 molar ratio of MTP to apoB. These results support a model in which: (1) the first 1000 amino acid residues of apoB are competent to complete the ''lipid pocket

  13. Associations between airway hyperresponsiveness, obesity, and lipoproteins in a longitudinal cohort

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Hancox, Robert; Nair, Parameswaran;

    2013-01-01

    . The present study investigated the association between airway hyperresponsiveness (AHR) to methacholine and body mass index (BMI) and plasma lipoproteins [low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol]. Methods Associations between AHR, BMI and plasma lipoproteins were...... assessed in a population-based cohort at ages 14 and 20 years. Results In unadjusted analyses, higher LDL cholesterol levels at age 14 were associated with AHR at age 20 in both sexes (P...

  14. Lipoprotein(a) as a cardiovascular risk factor : current status

    NARCIS (Netherlands)

    Nordestgaard, Børge G; Chapman, M John; Ray, Kausik; Borén, Jan; Andreotti, Felicita; Watts, Gerald F; Ginsberg, Henry; Amarenco, Pierre; Catapano, Alberico; Descamps, Olivier S; Fisher, Edward; Kovanen, Petri T; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne

    2010-01-01

    AIMS: The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies. METHODS AND RESULTS: The robust and specific association between e

  15. Low-density lipoprotein cholesterol and risk of gallstone disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  16. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target.

  17. A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

    Directory of Open Access Journals (Sweden)

    Scott J Cameron

    Full Text Available High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC. Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis.

  18. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... of lipid transfer from the mother to the developing fetus....

  19. Effects of progestational agents on serum lipids and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.

    1982-08-01

    Though progestins with relatively strong androgenic or antiestrogenic effects (e.g., levonorgestrel and norethindrone acetate) tend to have the greatest capacity to offset the major estrogen effects (e.g., on serum triglyceride and, to a greater extent, HDL-cholesterol), this association is not sufficiently strong to allow prediction of the effects of other progestins on lipid and lipoprotein metabolism.

  20. Interaction of low density lipoproteins with rat liver cells

    NARCIS (Netherlands)

    L. Harkes (Leendert)

    1985-01-01

    textabstractThe most marked conclusion is the establishment of the important role of non-parenchymal cells in the catabolism of the low density lipoproteins by the rat liver. Because the liver is responsible for 70-80% of the removal of LDL from blood this conclusion can be extended to total LDL tur

  1. Lifecycle of a Lipoprotein from a Biophysical Perspective

    Science.gov (United States)

    Rutledge, John C.; Huser, Thomas; Voss, John; Chan, James; Parikh, Atul

    The goal of our project was to understand how lipids and lipoproteins interact with cell membranes. This chapter will present the five major areas in which we have focused our attention on understanding how lipids and lipoproteins interact with cell membranes (Fig. 11.1): (1) triglycerides and vascular injury, (2) single lipoprotein analysis, (3) apolipoprotein E (apoE) conformation changes in the postprandial state, (4) triglyceride-rich lipoproteins (TGRLs) and endothelial cell inflammation, and (5) TGRL lipolysis products and monocyte activation. For over a hundred years, Western civilization has questioned how the food we eat translates into disease, and specifically atherosclerotic cardiovascular disease. Although most information indicates that this basic pathophysiological process is mediated through consumption of excess saturated fats, much remains unknown. After humans eat a meal, there is an elevation of triglycerides in the blood in the postprandial state. In normal individuals, triglycerides can rise after a meal by 50 to 100%. This has been documented many times in the past, including a paper by Hyson et al, (1998) [1]. In that study, normal healthy individuals were given a 40%-fat meal. Plasma triglycerides, which were modestly elevated initially, rose about 60% higher three to four hours after ingestion of the meal. Subsequently plasma triglycerides fell to baseline levels six hours after the meal. Even in these healthy individuals, a significant elevation of triglycerides was noted after ingestion of a moder ately high-fat meal.

  2. 21 CFR 862.1475 - Lipoprotein test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein test system. 862.1475 Section 862.1475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  3. DMPD: Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9287290 Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cell...9287290 Title Lipoprotein trafficking in vascular cells. Molecular Trojan horses ...ularsaboteurs. Hajjar DP, Haberland ME. J Biol Chem. 1997 Sep 12;272(37):22975-8. (.png) (.svg) (.html) (.csml) Show Lipoprotein traf...ficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. PubmedID

  4. Pitavastatin versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias.

    Science.gov (United States)

    Roever, Leonardo

    2016-05-01

    Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and are believed to be strongly atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be associated with endothelial dysfunction and atherosclerotic disease.

  5. Elevated Lipoprotein(A Impairs Platelet Radiolabeling Yield

    Directory of Open Access Journals (Sweden)

    Susanne Granegger

    2015-02-01

    Full Text Available Objectives: Platelet radiolabeling in clinical routine usually results in labeling efficiencies (LE above 80%. A variety of risk factors and clinical conditions are known to impair platelet labeling yield, among them elevated triglycerides and low-density lipoproteins. The potential influence of lipoprotein(a (Lp(a, an atherogenic lipoprotein particle containing a kringle subunit, which is widely found in the proteins of fibrinolysis pathway, has never been studied. Normal Lp(a levels range below 30 mg/ dl. The exact prevalence of elevated Lp(a is unknown, most likely ranging below 10%. Even more rare is an isolated elevation despite an otherwise normal lipoprotein profile. Methods: We examined the role of isolated elevated Lp(a (> 50 mg/dl, ranging up to 440 mg/dl compared to patients with normal lipid profile. Platelets were radiolabeled with in-111-oxine at 37 °C for 5 minutes using ISORBE-consensus methodology. Results: The findings indicate that already at levels below 100 mg/dl Lp(a decreases LE. LE assessment after cross-incubation of hyper-Lp(a platelets with normal Lp(a plasma and vice versa reveals that platelets rather than the plasmatic environment are responsible for the deterioration of labeling yield. This behavior already has been reported for elevated low-density lipoproteins. Apparently, the quantitative influence of LDL and Lp(a/mg is comparable. Plotting the sum of LDL and Lp(a versus LE reveals a clear significant negative correlation. Conclusion: As extremely elevated Lp(a, particularly above 150 mg/dl, may significantly impair labeling results. We therefore recommend to include extremely elevated Lp(a into the list of parameters, which should be known before performing radiolabeling of human platelets.

  6. Giardia lamblia low-density lipoprotein receptor-related protein is involved in selective lipoprotein endocytosis and parasite replication.

    Science.gov (United States)

    Rivero, Maria R; Miras, Silvana L; Quiroga, Rodrigo; Rópolo, Andrea S; Touz, Maria C

    2011-03-01

    As Giardia lamblia is unable to synthesize cholesterol de novo, this steroid might be obtained from the host's intestinal milieu by endocytosis of lipoproteins. In this work, we identified a putative Giardia lamblia low-density lipoprotein receptor-related proteins (GlLRP), a type I membrane protein, which shares the substrate N-terminal binding domain and a FXNPXY-type endocytic motif with human LRPs. Expression of tagged GlLRP showed that it was localized predominantly in the endoplasmic reticulum, lysosomal-like peripheral vacuoles and plasma membrane. However, the FXNPXY-deleted GlLRP was retained at the plasma membrane suggesting that it is abnormally transported and processed. The low-density lipoprotein and chylomicrons interacted with GlLRP, with this interaction being necessary for lipoprotein internalization and cell proliferation. Finally, we show that GlLRP binds directly to the medium subunit of Giardia adaptor protein 2, indicating that receptor-mediated internalization occurs through an adaptin mechanism.

  7. On a New Species of Phyllodistomum Braun, 1899 (Digenea: Gorgoderidae, a Parasite of Fresh Water Fish, Channa Punctatus (Bl. from Betwa River, Bundelkhand Region Jhansi, U.P, India.

    Directory of Open Access Journals (Sweden)

    Jag Mohan Sen

    2014-04-01

    Full Text Available The present paper deals with a new species of genus Phyllodistum Braun, 1899. Phyllodistomum betwaensis sp.n. is reported from fresh water fish Channa punctatus (Bl. from Betwa river, Bundelkhand region,Jhansi. It differs from all the earlier reported species in having the body of fluke is spatulate and dorso-ventrally flattened; anterior portion of body is long and curved while posterior portion of body is broad; slightly curved, tubular oesophagus: ventral sucker oval and larger than oral sucker; testes, post-equatorial, inter-caecal, anterior testis is larger than posterior one and parallel to ovary; ovary, oval, just behind right vitelline lobe, parallel to anterior testis; vitelline lobes posterior-lateral to ventral sucker, oval. Right vitelline lobe is larger than left vitelline lobe; eggs are oval and non-operculated.

  8. The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A.

    Science.gov (United States)

    Kounnas, M Z; Morris, R E; Thompson, M R; FitzGerald, D J; Strickland, D K; Saelinger, C B

    1992-06-25

    The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2 MR/LRP) is a large cell-surface glycoprotein consisting of a 515-kDa and an 85-kDa polypeptide; this receptor is thought to be responsible for the binding and endocytosis of activated alpha 2-macroglobulin and apoE-enriched beta-very low density lipoprotein. A similar high molecular weight glycoprotein has been identified as a potential receptor for Pseudomonas exotoxin A (PE). We demonstrate that the alpha 2 MR/LRP and the PE-binding glycoprotein have a similar mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and are immunologically indistinguishable. Furthermore, affinity-purified alpha 2 MR/LRP binds specifically to PE but not to a mutant toxin defective in its ability to bind cells. The 39-kDa receptor-associated protein, which blocks binding of ligands to alpha 2 MR/LRP, also prevents binding and subsequent toxicity of PE for mouse fibroblasts. The concentration of receptor-associated protein that was required to reduce binding and toxicity to 50% was approximately 14 nM, a value virtually identical to the KD measured for the interaction of receptor-associated protein with the purified receptor. Overall, the studies strongly suggest that the alpha 2 MR/LRP is responsible for internalizing PE.

  9. Segments in the C-terminal folding domain of lipoprotein lipase important for binding to the low density lipoprotein receptor-related protein and to heparan sulfate proteoglycans

    DEFF Research Database (Denmark)

    Nielsen, Morten Schallburg; Brejning, Jeanette; García, R.;

    1997-01-01

    Lipoprotein lipase (LpL) can mediate cellular uptake of chylomicron and VLDL remnants via binding to heparan sulfate proteoglycans (HSPG) and the endocytic alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2MR/LRP). Whereas it is established that the C-terminal ......Lipoprotein lipase (LpL) can mediate cellular uptake of chylomicron and VLDL remnants via binding to heparan sulfate proteoglycans (HSPG) and the endocytic alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha2MR/LRP). Whereas it is established that the C...

  10. Lipoprotein(a) and risk of myocardial infarction--genetic epidemiologic evidence of causality

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2011-01-01

    Elevated levels of lipoprotein(a) are associated with an increased risk of myocardial infarction. Our study aimed to test whether genetic data are consistent with this association being causal. Accordingly, we developed a high-throughput realtime PCR assay to genotype for the lipoprotein(a) kringle...... effect on plasma levels of lipoprotein(a). The association of LPA KIV-2 genotypes raising plasma levels of lipoprotein(a) with increased risk of myocardial infarction strongly supports a causal association of lipoprotein(a) with risk of myocardial infarction....

  11. Christina von Braun, Dorothea Dornhof, Eva Johach (Hg.: Das Unbewusste. Krisis und Kapital der Wissenschaften. Studien zum Verhältnis von Wissen und Geschlecht. Bielefeld: transcript Verlag 2009.

    Directory of Open Access Journals (Sweden)

    Zara Simone Pfeiffer

    2010-07-01

    Full Text Available Wissenschaft, die den Anspruch hat selbstreflexiv zu sein, sollte ihre unbewussten Anteile nicht ausblenden – das wird in den Beiträgen des von Christina von Braun, Dorothea Dornhof und Eva Johach herausgegebenen Sammelbandes auf überzeugende Weise gezeigt. Dabei geht es nicht primär um das Unbewusste als Objekt der Wissenschaften, sondern vielmehr um die Rolle des Unbewussten als Subjekt der Wissensordnung und Wissensproduktion, als „Krisis und Kapital“ der Wissenschaften, gleichermaßen als Sand und Öl imWissensgetriebe. Anstelle eines systematischen Überblicks liefert der interdisziplinär angelegte Band eine Vielzahl kluger, manchmal überraschender und durchgehend lesenswerter Perspektiven auf das visuelle und politische Unbewusste, seine Wissensgeschichte und seinen Ort in der Wissensordnung.Science, which purports to be self-reflexive, should not ignore its unconscious element – this is convincingly proven in the collected volume edited by Christina von Braun, Dorothea Dornhof, and Eva Johach. The focus is not merely on the unconscious as an object of the sciences, but on the role of the unconscious as a subject of knowledge organization and knowledge production, as “crisis and capital” of the sciences, indeed simultaneously functioning as sand and oil in the transmission of knowledge. In place of a systematic overview, the interdisciplinary volume offers a number of clever, sometimes surprising, and always well-worth reading perspectives on the visual and political unconscious, its history of knowledge, and its place in the order of knowledge.

  12. Sorting of bacterial lipoproteins to the outer membrane by the Lol system.

    Science.gov (United States)

    Narita, Shin-ichiro; Tokuda, Hajime

    2010-01-01

    Bacterial lipoproteins comprise a subset of membrane proteins with a lipid-modified cysteine residue at their amino termini through which they are anchored to the membrane. In Gram-negative bacteria, lipoproteins are localized on either the inner or the outer membrane. The Lol system is responsible for the transport of lipoproteins to the outer membrane.The Lol system comprises an inner-membrane ABC transporter LolCDE complex, a periplasmic carrier protein, LolA, and an outer membrane receptor protein, LolB. Lipoproteins are synthesized as precursors in the cytosol and then translocated across the inner membrane by the Sec translocon to the outer leaflet of the inner membrane, where lipoprotein precursors are processed to mature lipoproteins. The LolCDE complex then mediates the release of outer membrane-specific lipoproteins from the inner membrane while the inner membrane-specific lipoproteins possessing Asp at position 2 are not released by LolCDE because it functions as a LolCDE avoidance signal, causing the retention of these lipoproteins in the inner membrane. A water-soluble lipoprotein-LolA complex is formed as a result of the release reaction mediated by LolCDE. This complex traverses the hydrophilic periplasm to reach the outer membrane, where LolB accepts a lipoprotein from LolA and then catalyzes its incorporation into the inner leaflet of the outer membrane.

  13. Interplay between basic residues of hepatitis C virus glycoprotein E2 with viral receptors, neutralizing antibodies and lipoproteins.

    Science.gov (United States)

    Koutsoudakis, George; Dragun, Jakub; Pérez-Del-Pulgar, Sofia; Coto-Llerena, Mairene; Mensa, Laura; Crespo, Gonzalo; González, Patricia; Navasa, Miquel; Forns, Xavier

    2012-01-01

    Positively-charged amino acids are located at specific positions in the envelope glycoprotein E2 of the hepatitis C virus (HCV): two histidines (H) and four arginines (R) in two conserved WHY and one RGERCDLEDRDR motifs, respectively. Additionally, the E2 hypervariable region 1 (HVR1) is rich in basic amino acids. To investigate the role(s) of these residues in HCV entry, we subjected to comparative infection and sedimentation analysis cell culture-produced (HCVcc, genotype 2a) wild type virus, a panel of alanine single-site mutants and a HVR1-deletion variant. Initially, we analyzed the effects of these mutations on E2-heparan sulfate (HS) interactions. The positive milieu of the HVR1, formulated by its basic amino acids (key residues the conserved H³⁸⁶ and R⁴⁰⁸), and the two highly conserved basic residues H⁴⁸⁸ and R⁶⁴⁸ contributed to E2-HS interactions. Mutations in these residues did not alter the HCVcc-CD81 entry, but they modified the HCVcc-scavenger receptor class B type I (SR-BI) dependent entry and the neutralization by anti-E2 or patients IgG. Finally, separation by density gradients revealed that mutant viruses abolished partially or completely the infectivity of low density particles, which are believed to be associated with lipoproteins. This study shows that there exists a complex interplay between the basic amino acids located in HVR1 and other conserved E2 motifs with the HS, the SR-BI, and neutralizing antibodies and suggests that HCV-associated lipoproteins are implicated in these interactions.

  14. Distinct Hepatic Receptors for Low Density Lipoprotein and Apolipoprotein E in Humans

    Science.gov (United States)

    Hoeg, Jeffrey M.; Demosky, Stephen J.; Gregg, Richard E.; Schaefer, Ernst J.; Brewer, H. Bryan

    1985-02-01

    Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

  15. Biological and virulence characteristics of the YqhC mutant of Salmonella.

    Science.gov (United States)

    Eakley, Nicholas M; Bochsler, Philip N; Gopal Reddy, P; Chopra, Ashok K; Fadl, Amin A

    2011-12-01

    Previous work by the present authors indicated a murein lipoprotein mutant of Salmonella shows a marked down-regulation in expression of yqhC. Because YqhC is a putative DNA-binding protein, it is likely involved in modulation of Salmonella genes. Deletion of yqhC renders Salmonella defective in invasion of intestinal epithelial cells, motility, and induction of cytotoxicity. In the present study, further attenuation in induction of inflammatory cytokines/chemokines and histopathological lesions was seen in mice infected with the yqhC mutant. On the other hand, deletion of yqhC did not significantly affect the LD(50) in mice or the ability of Salmonella to survive and replicate in vivo. To better understand how YqhC affects Salmonella virulence and to identify factors potentially modulated by YqhC, comparative transcriptome and proteome analysis of the yqhC mutant and the WT Salmonella was performed. Data from these experiments indicate that deletion of yqhC significantly alters the transcription of several genes associated with the SPI-1 encoded T3SS and flagellar regulons, correlating with the yqhC mutant phenotype. Overall, this study indicates that deletion of the yqhC gene causes a number of virulence-related defects in vitro, but has a modest effect in vivo, despite affecting induction of inflammatory cytokines and histopathology.

  16. Bacterial mutants for enhanced succinate production

    NARCIS (Netherlands)

    Baart, G.J.E.; Beauprez, J.J.R.; Foulquie, M.M.R.; Heijnen, J.J.; Maertens, J.

    2010-01-01

    The present invention relates to a method for obtaining enhanced metabolite production in micro-organisms, and to mutants and/or transformants obtained with said method. More particularly, it relates to bacterial mutants and/or transformants for enhanced succinate production, especially mutants and/

  17. Problem-Solving Test: Tryptophan Operon Mutants

    Science.gov (United States)

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  18. Differential lipid binding of truncation mutants of Galleria mellonella apolipophorin III.

    Science.gov (United States)

    Dettloff, Matthias; Niere, Marc; Ryan, Robert O; Luty, Robert; Kay, Cyril M; Wiesner, Andreas; Weers, Paul M M

    2002-07-30

    Apolipophorin III (apoLp-III) is a prototype exchangeable apolipoprotein that is amenable to structure-function studies. The protein folds as a bundle of five amphipathic alpha-helices and undergoes a dramatic conformational change upon lipid binding. Recently, we have shown that a truncation mutant of Galleria mellonella apoLp-III comprising helices 1-3 is stable in solution and able to bind to lipid surfaces [Dettloff, M., Weers, P. M. M., Niere, M., Kay, C. M., Ryan, R. O., and Wiesner, A. (2001) Biochemistry 40, 3150-3157]. To investigate the role of the C-terminal helices in apoLp-III structure and function, two additional 3-helix mutants were designed: a core fragment comprising helix (H) 2-4, and a C-terminal fragment (H3-5). Each truncation mutant retained the ability to associate spontaneously with dimyristoylphosphatidylcholine (DMPC) vesicles, transforming them into discoidal complexes. The rate of apolipoprotein-dependent DMPC vesicle transformation decreased in the order H1-3 > H2-4 > H3-5. Truncation of two helices led to a significant decrease in alpha-helical content in buffer in each case, from 86% (wild-type) to 50% (H1-3), 28% (H2-4), and 24% alpha-helical content (H3-5). On the other hand, trifluoroethanol or complexation with DMPC induced the truncation mutants to adopt a high alpha-helical structure similar to that of wild-type protein (84-100% alpha-helical structure). ApoLp-III(H1-3) and apoLp-III(H2-4), but not apoLp-III(H3-5), were able to prevent phospholipase-C-induced low density lipoprotein aggregation, indicating that interaction of the C-terminal fragment with spherical lipoprotein surfaces was impaired. As lipoprotein binding is significantly affected and DMPC transformation rates are relatively slow upon removal of N-terminal helices, the data indicate that structural elements necessary for lipid interaction reside in the N-terminal part of the protein.

  19. Pharmacogenetic interaction between dexamethasone and Cd36-deficient segment of spontaneously hypertensive rat chromosome 4 affects triacylglycerol and cholesterol distribution into lipoprotein fractions.

    Science.gov (United States)

    Krupková, Michaela; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Kren, Vladimír; Seda, Ondrej

    2010-04-16

    Dexamethasone (DEX) is known to induce diabetes and dyslipidemia. We have compared fasting triacylglycerol and cholesterol concentrations across 20 lipoprotein fractions and glucose tolerance in control (standard diet) and DEX-treated 7-month-old males of two rat strains, Brown Norway (BN) and congenic BN.SHR-(Il6-Cd36)/Cub (BN.SHR4). These two inbred strains differ in a defined segment of chromosome 4, originally transferred from the spontaneously hypertensive rat (SHR) including the mutant Cd36 gene, a known target of DEX. Compared to BN, the standard-diet-fed BN.SHR4 showed higher cholesterol and triacylglycerol concentrations across many lipoprotein fractions, particularly in small VLDL and LDL particles. Total cholesterol was decreased by DEX by more than 21% in BN.SHR4 contrasting with the tendency to increase in BN (strain*DEX interaction p = 0.0017). Similar pattern was observed for triacylglycerol concentrations in LDL. The LDL particle size was significantly reduced by DEX in both strains. Also, while control BN and BN.SHR4 displayed comparable glycaemic profiles during oral glucose tolerance test, we observed a markedly blunted DEX induction of glucose intolerance in BN.SHR4 compared to BN. In summary, we report a pharmacogenetic interaction between limited genomic segment with mutated Cd36 gene and dexamethasone-induced glucose intolerance and triacylglycerol and cholesterol redistribution into lipoprotein fractions.

  20. [Lipoprotein metabolism in menopause. Effect of hormonal substitution therapy].

    Science.gov (United States)

    Heckers, H; Platt, D

    1991-06-20

    Oral administration of conjugated estrogens, estradiol valerate and micronized estradiol--but not the percutaneous application--in the postmenopause modifies the plasmic lipoprotein profile by lowering, dose-dependently, LDL and elevating HDL (HDL2). In parallel, the cardiovascular mortality is decreased by 50-66%, with smokers also benefiting to the same extent. On account of the increased risk for endometrial carcinoma associated with postmenopausal estrogen monotherapy, combination with a lowest-dose gestagen is imperative. However, the very numerous synthetic gestagens can antagonize the favorable effects of the estrogen on lipoprotein metabolism. This applies in particular to the gestagens of the 19-nortestosterone type, such as norethisterone acetate and, in particular, levonorgestrel, but less so the 17-hydroxyprogesterone derivatives medroxyprogesterone acetate and medrogestone with their very low androgenic effect.

  1. [Various lipoprotein fractions and their relation to ischemic heart disease].

    Science.gov (United States)

    Palazzuoli, V; Mondillo, S; Kristodhullu, A; De Stefano, R; Amatucci, G

    1983-01-01

    In a study carried out on over 700 patients with three different manifestations of aterosclerosis (cerebrovascular, coronary and peripheral), we could not find any statistically significant difference between the total cholesterol and triglyceride concentration in these three groups. Also, there was o difference in cholesterol and triglyceride levels between these three groups and 200 normal subjects. The same held true when we compared a selected group of 76 patients with ischaemic heart disease who had no other risk factor, with a group of 80 control subjects. On the contrary, when we compared several fractions of serum lipoproteins and the ratios of apolipoprotein A to Apolipoprotein B, LDL Cholesterol to HDL Cholesterol, and total Cholesterol to HDL Cholesterol of the two groups, the differences were statistically significant. We conclude that when other risk factors are excluded, the protein component, rather than the lipid component of the plasma lipoproteins correlates the presence of coronary artery disease.

  2. Oxidized low-density lipoprotein in postmenopausal women

    DEFF Research Database (Denmark)

    Jankowski, Vera; Just, Alexander R; Pfeilschifter, Johannes;

    2014-01-01

    of this study was to determine the prevalence of serum oxLDL in postmenopausal women and to identify possible associations of clinical and laboratory features with oxLDL in these patients. METHOD: After clinical examination and completing a clinical questionnaire, an ultrasound examination of both carotid.......10-0.43). Although intima-media thickness did not differ, postmenopausal women with serous oxLDL had more often atherosclerotic plaques compared to women without oxLDL (6/66 vs. 0/467; P high-density lipoprotein, impaired glucose intolerance, and DBP were independently associated...... with the occurrence of oxLDL. If oxLDL was present, higher high-density lipoprotein and glucose intolerance were associated with higher concentrations of oxLDL. In contrast, higher blood urea concentrations were associated with lower concentrations of oxLDL. CONCLUSION: This study presents the prevalence...

  3. Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

    Directory of Open Access Journals (Sweden)

    Klementina Fon Tacer

    2011-01-01

    Full Text Available Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver, through nonalcoholic steatohepatitis (NASH to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD, and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.

  4. Transgenic rabbit that expresses a functional human lipoprotein (a)

    Science.gov (United States)

    Rouy, Didier; Duverger, Nicolas; Emmanuel, Florence; Denefle, Patrice; Houdebine, Louis-Marie; Viglietta, Celine; Rubin, Edward M.; Hughes, Steven D.

    2003-01-01

    A transgenic rabbit which has in its genomic DNA sequences that encode apolipoprotein (a) and apolipoprotein B polypeptides which are capable of combining to produce lipoprotein (a), a process for creating such a rabbit, and the use of the rabbit to identify compounds which are effective in the treatment of human diseases which are associated with, induced and/or exacerbated by Lp(a) expression.

  5. Methods for studying rodent intestinal lipoprotein production and metabolism

    OpenAIRE

    Kohan, Alison B.; Howles, Philip N.; Tso, Patrick

    2012-01-01

    Lipid absorption begins with the digestion of dietary triacylglycerol and ultimately results in the secretion of triacylglycerol in chylomicrons into the lymphatics. Additionally, the intestine also secretes numerous proteins and peptides involved in lipid and lipoprotein metabolism in response to food. Ultimately, chylomicrons and these proteins, peptides, and hormones are found in lymph. The lymph fistula rat model has traditionally been used to study this intestinal absorption of nutrients...

  6. Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jerry D. Glickson

    2008-03-01

    Full Text Available Low-density lipoprotein (LDL provides a highly versatile natural nanoplatform for delivery of visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI contrast agents and photodynamic therapy and chemotherapeutic agents to normal and neoplastic cells that overexpress low-density lipoprotein receptors (LDLRs. Extension to other lipoproteins ranging in diameter from about 10 nm (high-density lipoprotein [HDL] to over a micron (chylomicrons is feasible. Loading of contrast or therapeutic agents onto or into these particles has been achieved by protein loading (covalent attachment to protein side chains, surface loading (intercalation into the phospholipid monolayer, and core loading (extraction and reconstitution of the triglyceride/cholesterol ester core. Core and surface loading of LDL have been used for delivery of optical imaging agents to tumor cells in vivo and in culture. Surface loading was used for delivery of gadolinium-bis-stearylamide contrast agents for in vivo MRI detection in tumor-bearing mice. Chlorin and phthalocyanine near-infrared photodynamic therapy agents (≤ 400/LDL have been attached by core loading. Protein loading was used to reroute the LDL from its natural receptor (LDLR to folate receptors and could be used to target other receptors. A semisynthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles with carboxylated cholesterol and overlaying a monolayer of phospholipid to which apolipoprotein A1 or E was adsorbed for targeting HDL or adsorbing synthetic amphipathic helical peptides ltargeting LDL or folate receptors. These particles can be used for in situ loading of magnetite into cells for MRI-monitored cell tracking or gene expression.

  7. Lipoprotein Modification by Advanced Glycosylation Endproducts (AGEs): Role in Atherosclerosis.

    Science.gov (United States)

    Bucala, R

    1997-02-01

    Recent progress in our understanding of advanced glycosylation reactions in vivo has affirmed the hypothesis that these products play an important role in the evolution of both diabetic and nondiabetic vascular disease. Utilizing newly developed advanced glycosylation end-products (AGE)-specific enzyme-linked immunosorbent assay (ELISA) techniques, AGEs have been identified to be present on a variety of vascular wall, lipoprotein, and lipid constituents. Vascular wall AGEs contribute to vascular pathology by increasing vascular permeability, enhancing subintimal protein and lipoprotein deposition, and inactivating nitric oxide. Lipid-linked AGEs present in low-density lipoprotein (LDL) also have been shown to initiate oxidative modification, promoting oxidation reactions that may proceed without the involvement of free metals or other radical generating systems. AGE-specific ELISA analysis has demonstrated a significantly increased level of AGE-modified LDL in the plasma of diabetic patients when compared to normal controls. AGE-modification impairs LDL-receptor-mediated clearance mechanisms in vivo and may contribute to elevated LDL levels in patients with diabetes. This concept has been substantiated further by the recent clinical observations that administration of the advanced glycosylation inhibitor aminoguanidine to diabetic patients significantly decreases circulating LDL levels. (Trends Cardiovasc Med 1997;7:39-47). © 1997, Elsevier Science Inc.

  8. Functional Roles of the Interaction of APP and Lipoprotein Receptors

    Science.gov (United States)

    Pohlkamp, Theresa; Wasser, Catherine R.; Herz, Joachim

    2017-01-01

    The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD.

  9. Characteristics of Lipoprotein Peak x Eluted from a Column with the Eluent of High-magnesium Ion Concentration in Lipoprotein Analysis Using the Cation-exchange Chromatography

    Directory of Open Access Journals (Sweden)

    Yuji Hirowatari

    2005-01-01

    Full Text Available The new lipoprotein analysis method using a cation-exchange chromatography, which contains a sulfopropyl-ligand column and two magnesium ion-containing eluents was previously reported. This method can separate serum lipoproteins on the column gel with a magnesium ion concentration gradient and high-density lipoprotein (HDL, low-density lipoprotein (LDL, very-low-density lipoprotein (VLDL and an unspecified lipoprotein peak are eluted in order from the column. We have now characterized the unspecified lipoproteins, designated peak x, which is last eluted from the column with the eluent of high-magnesium ion concentration. The peak x was small size chylomicron fraction with a part of VLDL. Furthermore, the cholesterol values in the peak x were significantly correlated with remnant-like particle (RLP-cholesterol values. The peak x separated from a hyperlipidemic patient included apolipoprotein B-100, B-48, E, A-1 and Cs (C-I, C-II, C-III and its composition of free cholesterol, cholesteryl esters, triglyceride (TG and phospholipids in total lipids were 6, 15, 66 and 13%, respectively. These results suggest that a major part of the lipoprotein peak X may be composed of remnants of chylomicron and VLDL, but it remains to be elucidated.

  10. Identification of a Long Rice Spikelet Mutant

    Institute of Scientific and Technical Information of China (English)

    WU Xian-jun; WANG Bin; HAN Zan-ping; XIE Zhao-hui; MOU Chun-hong; WANG Xu-dong

    2004-01-01

    A spontaneously occurring rice (Oryza sativa L. ) mutant, characterized by homeotic conversion in glumes and stamens, was found in the progeny of a cross. The mutant showed long glumes and glumaceous lodicules and morphological transformation of stamens into pistils. Mutant florets consisted of 1 to 3 completely developed pistils, some pistilloid stamens with filaments, but tipped by bulged tissue and 0 to 3 stigmas. It seens that the mutant phenotype of the homeotic conversions in glumes and stamens is similar to that of the B loss-of-function mutants in Arabidopsis and Antirrhinum. The mutant is controlled by a single recessive gene as a segregation ratio of 3:1 (wild type to mutant plants) was observed in the F2 generation.

  11. Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6 Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gwang-woong Go

    2015-06-01

    Full Text Available Low-density lipoprotein receptor-related protein 6 (LRP6 is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention.

  12. Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism

    DEFF Research Database (Denmark)

    Steiner, Carine; Holleboom, Adriaan G; Karuna, Ratna;

    2012-01-01

    distributions of the major 15 BA species and their precursor C4 (7a-hydroxy-4-cholesten-3-one). In normolipidaemic plasma, approximately 84%, 11% and 5% of BAs were recovered in the LPDS (lipoprotein-depleted serum), HDL and the combined LDL (low-density lipoprotein)/VLDL (very-low-density lipoproteins......) fraction respectively. Conjugated BAs were slightly over-represented in HDL. For C4, the respective percentages were 23%, 21% and 56% (41% in LDL and 15% in VLDL) respectively. Compared with unaffected family members, neither HDL-C (HDL-cholesterol)-decreasing mutations in the genes APOA1 [encoding Apo......BA (bile acid) formation is considered an important final step in RCT (reverse cholesterol transport). HDL (high-density lipoprotein) has been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein...

  13. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention

    Directory of Open Access Journals (Sweden)

    Jesús Millán

    2009-09-01

    Full Text Available Jesús Millán1, Xavier Pintó2, Anna Muñoz3, Manuel Zúñiga4, Joan Rubiés-Prat5, Luis Felipe Pallardo6, Luis Masana7, Alipio Mangas8, Antonio Hernández-Mijares9, Pedro González-Santos10, Juan F Ascaso11, Juan Pedro-Botet121Hospital Universitario Gregorio Marañón, Madrid, Spain; 2Hospital Universitario Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 3Solvay Pharma, Barcelona, Spain; 4Hospital Marqués de Valdecilla, Santander, Spain; 5Hospital Vall d’Hebrón, Barcelona, Spain; 6Hospital Universitario La Paz, Madrid, Spain; 7Hospital Sant Joan, Reus, Tarragona, Spain; 8Hospital Universitario Puerta del Mar, Cádiz, Spain; 9Hospital Universitario Dr Peset, Valencia, Spain; 10Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain; 11Hospital Clínico Universitario, Valencia, Spain; 12Hospital del Mar, Barcelona, SpainAbstract: Low-density lipoprotein (LDL cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or “atherogenic indices” have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol.Keywords: apolipoproteins

  14. Lipoprotein Kinetics in Male Hemodialysis Patients Treated with Atorvastatin

    Science.gov (United States)

    Schwaiger, Johannes P.; Nakada, Yoshinobu; Berberich, Ramona; Ikewaki, Katsunori; Dieplinger, Benjamin; Zitt, Emanuel; Neyer, Ulrich; Salmhofer, Hermann; Kronenberg, Florian; Koenig, Paul

    2013-01-01

    Summary Background and objectives In vivo metabolism of atherogenic apolipoprotein B (apoB)–containing lipoproteins is severely impaired in patients undergoing hemodialysis (HD), resulting in markedly prolonged residence times of these particles. It is unclear whether treatment with statins improves LDL kinetics in HD patients as is known for the general population. Therefore, this kinetic study assessed apoB-containing lipoproteins in these patients. Design, setting, participants, & measurements Kinetic measures were analyzed with stable-isotope technology in six men undergoing HD before and after 3 months of daily administration of 10 mg of atorvastatin. Patients were 18–65 years of age, had LDL cholesterol levels between 90 and 200 mg/dl, and had been treated with HD for >6 months. They consumed a standardized isocaloric diet for 3 days before analysis. Fractional catabolic rates (FCRs) and production rates of very-low-density lipoprotein (VLDL)–apoB, intermediate-density lipoprotein–apoB, and LDL-apoB were determined using multicompartment modeling after plasma lipoprotein separation, precipitation of apoB, and determination of tracer-to-tracee ratios using mass spectrometry. Results Plasma concentrations of VLDL- and LDL-apoB were significantly lower (mean ± SD, 7.77±2.62 versus 11.27±6.15 mg/dl, P<0.05; 56.9±23.9 versus 84.0±21.1 mg/dl, P=0.03) and their FCRs were significantly higher (7.20±3.08 versus 5.20±2.98 days−1, P<0.05; 0.851±0.772 versus 0.446±0.232 days−1, P<0.05) after 3 months of atorvastatin treatment. Accordingly, the residence times in plasma of VLDL- and LDL-apoB were significantly lower after treatment (0.14 versus 0.19 day and 1.2 versus 2.2 days, respectively). Conclusion Lower plasma concentrations and improved kinetics of atherogenic lipoproteins were observed in HD patients after administration of low-dose atorvastatin. PMID:23599405

  15. The membrane bound LRR lipoprotein Slr, and the cell wall-anchored M1 protein from Streptococcus pyogenes both interact with type I collagen.

    Directory of Open Access Journals (Sweden)

    Marta Bober

    Full Text Available Streptococcus pyogenes is an important human pathogen and surface structures allow it to adhere to, colonize and invade the human host. Proteins containing leucine rich repeats (LRR have been identified in mammals, viruses, archaea and several bacterial species. The LRRs are often involved in protein-protein interaction, are typically 20-30 amino acids long and the defining feature of the LRR motif is an 11-residue sequence LxxLxLxxNxL (x being any amino acid. The streptococcal leucine rich (Slr protein is a hypothetical lipoprotein that has been shown to be involved in virulence, but at present no ligands for Slr have been identified. We could establish that Slr is a membrane attached horseshoe shaped lipoprotein by homology modeling, signal peptidase II inhibition, electron microscopy (of bacteria and purified protein and immunoblotting. Based on our previous knowledge of LRR proteins we hypothesized that Slr could mediate binding to collagen. We could show by surface plasmon resonance that recombinant Slr and purified M1 protein bind with high affinity to collagen I. Isogenic slr mutant strain (MB1 and emm1 mutant strain (MC25 had reduced binding to collagen type I as shown by slot blot and surface plasmon resonance. Electron microscopy using gold labeled Slr showed multiple binding sites to collagen I, both to the monomeric and the fibrillar structure, and most binding occurred in the overlap region of the collagen I fibril. In conclusion, we show that Slr is an abundant membrane bound lipoprotein that is co-expressed on the surface with M1, and that both these proteins are involved in recruiting collagen type I to the bacterial surface. This underlines the importance of S. pyogenes interaction with extracellular matrix molecules, especially since both Slr and M1 have been shown to be virulence factors.

  16. Sorting of an integral outer membrane protein via the lipoprotein-specific Lol pathway and a dedicated lipoprotein pilotin.

    Science.gov (United States)

    Collin, Séverine; Guilvout, Ingrid; Nickerson, Nicholas N; Pugsley, Anthony P

    2011-05-01

    The lipoprotein PulS is a dedicated chaperone that is required to target the secretin PulD to the outer membrane in Klebsiella or Escherichia coli, and to protect it from proteolysis. Here, we present indirect evidence that PulD protomers do not assemble into the secretin dodecamer before they reach the outer membrane, and that PulS reaches the outer membrane in a soluble heterodimer with the general lipoprotein chaperone LolA. However, we could not find any direct evidence for PulD protomer association with the PulS-LolA heterodimer. Instead, in cells producing PulD and a permanently locked PulS-LolA dimer (in which LolA carries an R43L substitution that prevents lipoprotein transfer to LolB in the outer membrane), LolAR43L was found in the inner membrane, probably still associated with PulS bound to PulD that had been incorrectly targeted because of the LolAR43L substitution. It is speculated that PulD protomers normally cross the periplasm together with PulS bound to LolA but when the latter cannot be separated (due to the mutation in lolA), the PulD protomers form dodecamers that insert into the inner membrane.

  17. An increase in lipoprotein oxidation and endogenous lipid peroxides in serum of obese women.

    Science.gov (United States)

    Mutlu-Türkoğlu, U; Oztezcan, S; Telci, A; Orhan, Y; Aykaç-Toker, G; Sivas, A; Uysal, M

    2003-02-01

    Endogenous malondialdehyde and diene conjugate levels, the susceptibility of apolipoprotein B-containing lipoproteins to copper-induced lipid peroxidation, and antibody titer against oxidized low-density lipoproteins were increased, but serum antioxidant activity was unchanged in obese women. Serum cholesterol, low-density lipoproteincholesterol, and trigliceride levels were also elevated, but high-density lipoprotein-cholesterol levels remained unchanged in obese women. In vitro, oxidation of apolipoprotein B-containing lipoproteins and levels of antibody against oxidized low-density lipoprotein correlated with body mass index, serum total cholesterol, and low-density lipoproteincholesterol levels in obese women. These results indicate that obesity is associated with increases in endogenous lipid peroxides, oxidation of low-density lipoproteins, and lipids in serum.

  18. Staphylococcus aureus DsbA is a membrane-bound lipoprotein with thiol-disulfide oxidoreductase activity.

    Science.gov (United States)

    Dumoulin, Alexis; Grauschopf, Ulla; Bischoff, Markus; Thöny-Meyer, Linda; Berger-Bächi, Brigitte

    2005-11-01

    DsbA proteins, the primary catalysts of protein disulfide bond formation, are known to affect virulence and penicillin resistance in Gram-negative bacteria. We identified a putative DsbA homologue in the Gram-positive pathogen Staphylococcus aureus that was able to restore the motility phenotype of an Escherichia coli dsbA mutant and thus demonstrated a functional thiol oxidoreductase activity. The staphylococcal DsbA (SaDsbA) had a strong oxidative redox potential of -131 mV. The persistence of the protein throughout the growth cycle despite its predominant transcription during exponential growth phase suggested a rather long half-life for the SaDsbA. SaDsbA was found to be a membrane localised lipoprotein, supporting a role in disulfide bond formation. But so far, neither in vitro nor in vivo phenotype could be identified in a staphylococcal dsbA mutant, leaving its physiological role unknown. The inability of SaDsbA to interact with the E. coli DsbB and the lack of an apparent staphylococcal DsbB homologue suggest an alternative re-oxidation pathway for the SaDsbA.

  19. Lipoprotein N-acyl transferase (Lnt1) is dispensable for protein O-mannosylation by Streptomyces coelicolor.

    Science.gov (United States)

    Córdova-Dávalos, Laura Elena; Espitia, Clara; González-Cerón, Gabriela; Arreguín-Espinosa, Roberto; Soberón-Chávez, Gloria; Servín-González, Luis

    2014-01-01

    A protein glycosylation system related to that for protein mannosylation in yeast is present in many actinomycetes. This system involves polyprenyl phosphate mannose synthase (Ppm), protein mannosyl transferase (Pmt), and lipoprotein N-acyl transferase (Lnt). In this study, we obtained a series of mutants in the ppm (sco1423), lnt1 (sco1014), and pmt (sco3154) genes of Streptomyces coelicolor, which encode Ppm, Lnt1, and Pmt, to analyze their requirement for glycosylation of the heterologously expressed Apa glycoprotein of Mycobacterium tuberculosis. The results show that both Ppm and Pmt were required for Apa glycosylation, but that Lnt1 was dispensable for both Apa and the bacteriophage φC31 receptor glycosylation. A bacterial two-hybrid assay revealed that contrary to M. tuberculosis, Lnt1 of S. coelicolor does not interact with Ppm. The D2 catalytic domain of M. tuberculosisPpm was sufficient for complementation of an S. coelicolor double mutant lacking Lnt1 and Ppm, both for Apa glycosylation and for glycosylation of φC31 receptor. On the other hand, M. tuberculosisPmt was not active in S. coelicolor, even when correctly localized to the cytoplasmic membrane, showing fundamental differences in the requirements for Pmt activity in these two species.

  20. Recurrent Embolic Strokes of Undetermined Source in a Patient with Extreme Lipoprotein(a) Levels.

    Science.gov (United States)

    Bulwa, Zachary; Kim, Audrey; Singh, Karandeep; Kantorovich, Alexander; Suhail, Faten

    2016-01-01

    Lipoprotein(a) is a plasma lipoprotein and known cardiovascular risk factor, most recently implicated in the development of high-risk carotid atherosclerotic plaques without significant carotid stenosis. We present a case of a young African-American female with recurrent embolic strokes of undetermined source. After our thorough investigation, we identified the link between a small, irregular plaque in the right internal carotid artery, and an extremely elevated plasma level of lipoprotein(a) as the source of her embolic strokes.

  1. Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

    OpenAIRE

    Manfredi Rizzo; Mikhailidis, Dimitri P.; Isenovic, Esma R.; Dragana Nikolic; Niki Katsiki; Giuseppe Montalto

    2013-01-01

    Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) ...

  2. Characterization of the Pseudomonas aeruginosa Lol system as a lipoprotein sorting mechanism.

    Science.gov (United States)

    Tanaka, Shin-Ya; Narita, Shin-Ichiro; Tokuda, Hajime

    2007-05-04

    Escherichia coli lipoproteins are localized to either the inner or the outer membrane depending on the residue that is present next to the N-terminal acylated Cys. Asp at position 2 causes the retention of lipoproteins in the inner membrane. In contrast, the accompanying study (9) revealed that the residues at positions 3 and 4 determine the membrane specificity of lipoproteins in Pseudomonas aeruginosa. Since the five Lol proteins involved in the sorting of E. coli lipoproteins are conserved in P. aeruginosa, we examined whether or not the Lol proteins of P. aeruginosa are also involved in lipoprotein sorting but utilize different signals. The genes encoding LolCDE, LolA, and LolB homologues were cloned and expressed. The LolCDE homologue thus purified was reconstituted into proteoliposomes with lipoproteins. When incubated in the presence of ATP and a LolA homologue, the reconstituted LolCDE homologue released lipoproteins, leading to the formation of a LolA-lipoprotein complex. Lipoproteins were then incorporated into the outer membrane depending on a LolB homologue. As revealed in vivo, lipoproteins with Lys and Ser at positions 3 and 4, respectively, remained in proteoliposomes. On the other hand, E. coli LolCDE released lipoproteins with this signal and transferred them to LolA of not only E. coli but also P. aeruginosa. These results indicate that Lol proteins are responsible for the sorting of lipoproteins to the outer membrane of P. aeruginosa, as in the case of E. coli, but respond differently to inner membrane retention signals.

  3. In vitro lipid transfer between lipoproteins and midgut-diverticula in the spider Polybetes pythagoricus.

    Science.gov (United States)

    Laino, Aldana; Cunningham, Mónica L; Heras, Horacio; Garcia, Fernando

    2011-12-01

    It has been already reported that most hemolymphatic lipids in the spider Polybetes pythagoricus are transported by HDL1 and VHDL lipoproteins. We studied in vitro the lipid transfer among midgut-diverticula (M-diverticula), and either hemolymph or purified lipoproteins as well as between hemolymphatic lipoproteins. M-diverticula and hemolymph were labeled by in vivo (14)C-palmitic acid injection. In vitro incubations were performed between M-diverticula and either hemolymph or isolated lipoproteins. Hemolymph lipid uptake was associated to HDL1 (67%) and VHDL (32%). Release from hemolymph towards M-diverticula showed the opposite trend, VHDL 75% and HDL1 45%. Isolated lipoproteins showed a similar behavior to that observed with whole hemolymph. Lipid transfer between lipoproteins showed that HDL1 transfer more (14)C-lipids to VHDL than vice versa. Only 38% FFA and 18% TAG were transferred from M-diverticula to lipoproteins, while on the contrary 75% and 73% of these lipids, respectively, were taken up from hemolymph. A similar trend was observed regarding lipoprotein phospholipids. This study supports the hypothesis that HDL1 and hemocyanin-containing VHDL are involved in the uptake and release of FFA, phospholipids and triacylglycerols in the spider P. pythagoricus. The data support a directional flow of lipids from HDL1 and VHDL suggesting a mode of lipid transport between lipoproteins and M-diverticula.

  4. Macrophage uptake of a lipoprotein-sequestered toxicant: a potential route of immunotoxicity.

    Science.gov (United States)

    Kaminski, N E; Wells, D S; Dauterman, W C; Roberts, J F; Guthrie, F E

    1986-03-15

    An experimental system was chosen to investigate the bioactivity of a lipoprotein-sequestered toxicant at the cellular level based on recent studies demonstrating receptor-mediated uptake of lipoproteins by macrophages. Rat peritoneal exudate cell suspensions (PEC) were exposed to DDT and lipoprotein-sequestered DDT, followed by measurement of DDT uptake, metabolism, and cellular toxicity. In vitro uptake assays demonstrated that PEC suspensions treated for 10, 20, and 30 min with 2.5 microM lipoprotein-sequestered DDT had approximately a twofold increase over the amount of DDT associated with PEC treated with 2.5 microM free DDT. PEC were assayed for DDT metabolites to serve as a measure of the cellular internalization of the toxicant after treatment in vitro for 18 hr with either 1.5 microM DDT or lipoprotein-sequestered DDT. Evidence of DDT metabolism was only observed with PEC which had been treated with lipoprotein-sequestered DDT. These cells contained significantly higher amounts of DDT metabolites as compared to cells treated with unsequestered DDT (over an eightfold difference). Assays measuring macrophage phagocytic activity indicated that macrophages treated for 4.5 hr in vitro with 2.5 microM lipoprotein-sequestered DDT showed significant inhibition in their ability to phagocytize yeast particles. These results suggest that serum lipoproteins may facilitate the cellular uptake of lipoprotein-sequestered toxicants leading to altered cellular function (phagocytosis).

  5. In vitro studies on the distribution of probucol among human plasma lipoproteins.

    Science.gov (United States)

    Urien, S; Riant, P; Albengres, E; Brioude, R; Tillement, J P

    1984-09-01

    The role of human plasma lipoproteins as carriers in the blood transport of the cholesterol-lowering and water-insoluble drug, probucol, was investigated in in vitro studies. [14C]Probucol was incubated in whole human blood, a serum pool, individual diluted sera, and isolated protein and lipoprotein fractions. In whole blood, about 90% partitioned in plasma. Following ultracentrifugal fractionation of the serum, it was found that less than 5% distributed in the d greater than 1.20 protein fraction (albumin-rich fraction) and more than 95% in the lipoprotein fractions. The distribution of probucol in the lipoprotein fractions correlated with the lipoprotein total lipid volume under saturation conditions (incubation of isolated lipoprotein fractions) as well as nonsaturation conditions (fractionation of serum exposed to [14C]probucol). Incubation of the albumin-rich fraction and of apolipoproteins originating from the isolated lipoprotein fractions showed that they account for a negligible part in the interaction of probucol with blood components. The probucol uptake of individual sera was shown to be correlated to the lipid content of the serum. When probucol was incubated in erythrocyte suspensions containing variable amounts of lipoproteins, probucol partitioned less in erythrocytes as the lipoprotein concentration increased in the suspension.

  6. Recent advances in lipoprotein and atherosclerosis: A nutrigenomic approach

    Directory of Open Access Journals (Sweden)

    López, Sergio

    2009-03-01

    Full Text Available Atherosclerosis is a disease in which multiple factors contribute to the degeneration of the vascular wall. Many risk factors have been identified as having influence on the progression of atherosclerosis among them, the type of diet. Multifactorial interaction among lipoproteins, vascular wall cells, and inflammatory mediators has been recognised as the basis of atherogenesis. Dietary intake affects lipoprotein concentration and composition providing risk or protection at several stages of atherosclerosis. More intriguingly, it has been demonstrated that the extent to which each lipid or lipoprotein is associated with cardiovascular disease depends on the time to last meal; thus, postprandial lipoproteins, main lipoproteins in blood after a high-fat meal, have been shown to strongly influence atherogenesis. As a complex biological process, the full cellular and molecular characterization of atherosclerosis derived by diet, calls for application of the newly developing “omics” techniques of analysis. This review will considered recent studies using high-throughput technologies and a nutrigenomic approach to reveal the patho-physiological effects that the fasting and postprandial lipoproteins may exert on the vascular wall.La aterosclerosis es una enfermedad en la que múltiples factores, entre los que se encuentra la dieta, contribuyen a la degradación de la pared vascular. En la etiología de la aterogénesis son determinantes las lipoproteínas plasmáticas y los distintos tipos celulares de la pared vascular, incluyendo una respuesta inflamatoria. La ingesta de alimentos afecta la concentración y composición de las lipoproteínas, ejerciendo un papel de riesgo o protector durante las diferentes etapas del proceso aterosclerótico. Es importante destacar que la naturaleza de las lipoproteínas y por lo tanto su papel en la enfermedad cardiovascular, también depende del tiempo transcurrido entre comidas. Por ejemplo, las lipoprote

  7. Biochemical and histological characterization of tomato mutants

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    Carolina C. Monteiro

    2012-06-01

    Full Text Available Biochemical responses inherent to antioxidant systems as well morphological and anatomical properties of photomorphogenic, hormonal and developmental tomato mutants were investigated. Compared to the non-mutant Micro-Tom (MT, we observed that the malondialdehyde (MDA content was enhanced in the diageotropica (dgt and lutescent (l mutants, whilst the highest levels of hydrogen peroxide (H2O2 were observed in high pigment 1 (hp1 and aurea (au mutants. The analyses of antioxidant enzymes revealed that all mutants exhibited reduced catalase (CAT activity when compared to MT. Guaiacol peroxidase (GPOX was enhanced in both sitiens (sit and notabilis (not mutants, whereas in not mutant there was an increase in ascorbate peroxidase (APX. Based on PAGE analysis, the activities of glutathione reductase (GR isoforms III, IV, V and VI were increased in l leaves, while the activity of superoxide dismutase (SOD isoform III was reduced in leaves of sit, epi, Never ripe (Nr and green flesh (gf mutants. Microscopic analyses revealed that hp1 and au showed an increase in leaf intercellular spaces, whereas sit exhibited a decrease. The au and hp1 mutants also exhibited a decreased in the number of leaf trichomes. The characterization of these mutants is essential for their future use in plant development and ecophysiology studies, such as abiotic and biotic stresses on the oxidative metabolism.Neste trabalho, analisamos as respostas bioquímicas inerentes ao sistema antioxidante, assim como propriedades morfológicas e anatômicas de mutantes fotomorfogenéticos e hormonais de tomateiro. Comparados ao não mutante Micro-Tom (MT, observamos que o conteúdo de malondialdeído (MDA aumentou nos mutantes diageotropica (dgt e lutescent (l, enquanto os maiores níveis de H2O2 foram encontrados nos mutantes high pigment 1 (hp1 e aurea (au. Análises de enzimas antioxidantes mostraram que todos os mutantes reduziram a atividade de catalase (CAT quando comparado a MT. A

  8. Lipoprotein(a: Metabolismus und Beeinflussung des Plasmaspiegels

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    Kostner GM

    2002-01-01

    Full Text Available Lipoprotein(a [Lp(a] ist eines der atherogensten Lipoproteine. Es besteht aus einem Core Low Density Lipoprotein (LDL und dem spezifischen Antigen, Apo(a. Letzteres ist ein extrem polymorphes Glykoprotein, welches aus zwischen 11 und mehr als 40 Kringel-IV-Einheiten besteht, die homolog zum Kringel-IV des Plasminogens sind. Die Atherogenität von Lp(a, die einerseits auf seine Strukturähnlichkeit mit Plas-minogen, andererseits auf seine extrem hohe Affinität zu Proteoglykanen der Blutgefäße zurückzuführen ist, wurde in zahlreichen prospektiven Studien dokumentiert. Die Mittel- bzw. Medianwerte für Lp(a in der weißen Bevölkerung betragen 17 bzw. 9 mg/dl. Als Grenzwert, ab welchem ein erhöhtes Atheroskleroserisiko auftritt, gilt allgemein 25?30 mg/dl. Die Plasmakonzentration von Lp(a ist streng genetisch determiniert und korreliert negativ mit der Kringelzahl. Andererseits wird die Plasmakonzentration von der Syntheserate und nicht vom Katabolismus bestimmt. Hormone wie T3/T4, Steroid- und im besonderen Wachstumshormone und ILG-1 zeigen sehr deutliche Einflüsse auf den Lp(a-Metabolismus. Leberpatienten haben im Verhältnis zu ihrer Kringelzahl stark erniedrigte und Nierenpatienten stark erhöhte Plasma-Lp(a-Spiegel. Die stärkste pharmakologische Wirkung auf Lp(a haben anabole Steroide. Aber auch Alkohol, Acetylsalicylsäure, Ascorbinsäure und vor allem Nikotinsäure wirken Lp(a-senkend. Die herkömmlichen Lipidsenker zeigen - wenn überhaupt - nur eine geringe Wirkung. Bisher ist kein nennenswert Lp(a-senkendes Statin gefunden worden. Eine futuristische Möglichkeit, therapeutisch einzugreifen, wurde von uns mittels "anti-sense Oligonucleotide"-Therapie an Versuchstieren getestet. Es gelang damit, die Apo(a-Synthese praktisch auf Null zu senken.

  9. Correlation studies between serum concentrations of zinc and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Mitiko; Alves, Edson R.; Vasconcellos, M.B.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mitiko@ipen.br, e-mail: eralves@ipen.br, e-mail: mbvascon@ipen.br; Sumita, Nairo M. [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas.Central Lab. Division and Laboratories of Medical Investigation (LIM-03)], e-mail: dlc.bioquimica@hcnet.usp.br; Jaluul, Omar; Jacob-Filho, Wilson [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina], e-mail: jaluul@uol.com.br, wiljac@usp.br

    2009-07-01

    In this study, serum zinc and lipoprotein concentrations were determined in order to assess the health status of an elderly population residing in Sao Paulo city, SP, Brazil. This population consisted of elderly considered healthy and participating of a 'Successful Ageing' program of the Sao Paulo University Medical School. Fasting blood samples were collected from 87 elderly individuals (63 females and 24 males) aged 60-91 and mean age of 72 +- 7 years. Zn concentrations were determined by neutron activation analysis at the IPEN/CNEN/ SP and, the lipoprotein (HDL, LDL and total cholesterol) concentrations were determined using routine analysis methods of the Central Laboratory Division, Hospital das Clinicas, FMUSP. Results obtained for Zn indicated that all the individuals presented this element within the recommended value. For total cholesterol and HDL-cholesterol concentrations, 96 % of elderly presented levels within the desired range but for LDL cholesterol concentrations only about 70.0 % of individuals were in the desired range. Serum concentration of Zn were positively correlated to LDL-cholesterol levels (correlation coefficient r = 0.21, p < 0.06). Furthermore, the ratios of [HDL-cholesterol] / [LDL-cholesterol] were negatively correlated with Zn concentrations (r = - 0.234, p < 0.04). The positive correlation found between the serum concentrations of Zn and LDL-cholesterol indicates the possible effect of this element in serum lipoprotein profiles. Thus ,these findings suggest that more investigations should be conducted on Zn supplementation in elderly subjects with cardiovascular diseases. (author)

  10. Transport of phytanic acid on lipoproteins in Refsum disease.

    Science.gov (United States)

    Wierzbicki, A S; Sankaralingam, A; Lumb, P J; Hardman, T C; Sidey, M C; Gibberd, F B

    1999-02-01

    Patients with Refsum disease accumulate significant quantities of phytanic acid in adipose and neural tissue. The accumulation can be reversed by following a diet low in phytanic acid, yet the mechanism of transport of this fatty acid is obscure. We investigated the distribution of phytanic acid in different lipoprotein subfractions in 11 patients with Refsum disease and 9 unaffected siblings. Plasma phytanic acid was distributed on VLDL (16.2% +/- 12.2%), IDL (1.77% +/- 1.64%), LDL (34.8% +/- 12.6%) and HDL (14.3% +/- 7.87%). No correlations with any parameter were seen with total phytanic acid content. Weak nonsignificant correlations were found with the fractional distribution of phytanic acid and VLDL triglyceride (r = 0.35; p = 0.12) and plasma HDL-cholesterol (r = 0.32; p = 0.16) and with LDL:HDL cholesterol ratio (r = 0.33; p = 0.14). Significant correlation of the fractional distribution of phytanic acid on lipoprotein particles was noted with the ratio of apolipoprotein B: apolipoprotein A1-containing particles (r = 0.46; p = 0.03) and apolipoprotein B: apolipoprotein A1 in HDL2 (r = 0.53; p = 0.01). This suggests that the import-export balance for phytanic acid in plasma is related to forward and reverse cholesterol transport on lipoprotein particles, and only weakly to plasma cholesterol and triglycerides. These ratios of apolipoprotein particles may play a significant role in determining the rate of phytanic acid elimination in patients with Refsum disease.

  11. The influence of lipoprotein(a on fibrinolytic activity

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    Rahajuningsih D. Setiabudy

    2004-09-01

    Full Text Available Lipoprotein(a is a plasma lipoprotein whose structure and composition are similar with low density lipoprotein (LDL with an addition of apo(a that is bound to apo B100. The structure of apo(a is similar with plasminogen, a proenzym in fibrinolytic system. Due to this similarity, it is assumed that Lp(a can inhibit plasminogen activity and decreases fibrinolytic activity. The purpose of this study is to prove that addition of Lp(a to normal plasma can inhibit fibrinolytic activity. Four healthy people whose fibrinogen levels, plasminogen activities and euglobulin clot lysis time were within normal range were enrolled in this study. Fibrinolytic activity were assessed by euglobulin clot lysis time (ECLT. In the first experiment, the addition of Lp(a was done before centrifugation to obtain euglobulin precipitates, while in the second experiment, Lp(a was added to the euglobulin precipitates. As a control, ECLT was performed in the plasma with the addition of NaCl 0.9% in the same volume with Lp(a. The results of the study showed that in the first experiment, there was no clot formation. It is assumed that Lp(a can bind fibrinogen and both of them floated in the supernatant, so there was no fibrinogen in the euglobulin precipitate that can be clotted by thrombin. In the second experiment, the clot did not dissolve until the fourth day. In conclusion, the addition of Lp(a to normal plasma can inhibit the activity of fibrinolytic system. (Med J Indones 2004; 13: 135-9 Keywords: plasminogen, fibrinogen, apo(a, euglobulin clot lysis time (ECLT

  12. Lipoprotein apheresis in the management of severe hypercholesterolemia and of elevation of lipoprotein(a): current perspectives and patient selection

    Science.gov (United States)

    Julius, Ulrich

    2016-01-01

    This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail – major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated. Indications for LA therapy are quoted: homozygous familial hypercholesterolemia (HCH), severe HCH, and isolated elevation of Lp(a) and progress of atherosclerotic disease. A major focus is on the evidence of the effect of LA on cardiovascular outcome data, and the most important publications are cited in this context. The best studies have been performed in patients with elevated Lp(a) in whom cardiovascular events were reduced by more than 80%. Major adverse effects and contraindications are listed. The impact of an LA therapy on patient quality of life and the requirements they have to fulfill are also highlighted. Finally, the future role of LA in treating high-risk patients with high LDL-C and/or high Lp(a) is discussed. It is probable that the significance of LA for treating patients with elevated LDL-C will decrease (with the exception of homozygous familial HCH) due to the application of PCSK9 inhibitors. The antisense oligonucleotide against apolipoprotein(a) could replace LA in patients with high Lp(a), provided positive outcome data are generated. PMID:27785114

  13. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

    OpenAIRE

    Kathiresan, Sekar; Melander, Olle; Guiducci, Candace; Surti, Aarti; Burtt, Noël P.; Rieder, Mark J; Cooper, Gregory M.; Roos, Charlotta; Benjamin F Voight; Havulinna, Aki S.; Wahlstrand, Björn; Hedner, Thomas; Corella, Dolores; Tai, E Shyong; Ordovas, Jose M.

    2008-01-01

    Blood concentrations of lipoproteins and lipids are heritable1 risk factors for cardiovascular disease2,3. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue4) and targeted replication associat...

  14. Low density lipoproteins as circulating fast temperature sensors.

    Directory of Open Access Journals (Sweden)

    Ruth Prassl

    Full Text Available BACKGROUND: The potential physiological significance of the nanophase transition of neutral lipids in the core of low density lipoprotein (LDL particles is dependent on whether the rate is fast enough to integrate small (+/-2 degrees C temperature changes in the blood circulation. METHODOLOGY/PRINCIPAL FINDINGS: Using sub-second, time-resolved small-angle X-ray scattering technology with synchrotron radiation, we have monitored the dynamics of structural changes within LDL, which were triggered by temperature-jumps and -drops, respectively. Our findings reveal that the melting transition is complete within less than 10 milliseconds. The freezing transition proceeds slowly with a half-time of approximately two seconds. Thus, the time period over which LDL particles reside in cooler regions of the body readily facilitates structural reorientation of the apolar core lipids. CONCLUSIONS/SIGNIFICANCE: Low density lipoproteins, the biological nanoparticles responsible for the transport of cholesterol in blood, are shown to act as intrinsic nano-thermometers, which can follow the periodic temperature changes during blood circulation. Our results demonstrate that the lipid core in LDL changes from a liquid crystalline to an oily state within fractions of seconds. This may, through the coupling to the protein structure of LDL, have important repercussions on current theories of the role of LDL in the pathogenesis of atherosclerosis.

  15. Lipoprotein (a and cardiovascular risk factors in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ástrid Camêlo Palmeira

    2013-12-01

    Full Text Available OBJECTIVE: To review the relationship between lipoprotein (a [Lp(a] and other risk factors for cardiovascular disease (CVD in children and adolescents. DATA SOURCES: This systematic review included studies from 2001 to 2011, a ten-year time period. Epidemiological studies with children and/or adolescents published in English, Portuguese or Spanish and fully available online were included. The searches were performed in Science Direct, PubMed/Medline, BVS (Biblioteca Virtual em Saúde and Cochrane Library databases, using the following combination of key-words: "lipoprotein a" and "cardiovascular diseases" and "obesity". DATA SYNTHESIS: Overall, 672 studies were obtained but only seven were included. Some studies assessed the family history for CVD. In all of them, Lp(a levels were increased in patients with family history for CVD. There was also a positive correlation between Lp(a and LDL-cholesterol, total cholesterol, and apolipoprotein B levels, suggesting an association between Lp(a levels and the lipid profile. CONCLUSIONS: The evidence that CVD may originate in childhood and adolescence leads to the need for investigating the risk factors during this period in order to propose earlier and possibly more effective interventions to reduce morbidity and mortality rates.

  16. Lipid profiling of lipoprotein X: Implications for dyslipidemia in cholestasis.

    Science.gov (United States)

    Heimerl, Susanne; Boettcher, Alfred; Kaul, Harald; Liebisch, Gerhard

    2016-08-01

    Lipoprotein X (Lp-X) is an abnormal lipoprotein that may typically be formed in intra- and extrahepatic cholestasis and potentially interfere with lipid analysis in the routine lab. To gain insight into lipid class and species composition, Lp-X, LDL and HDL from cholestatic and control serum samples were subjected to mass spectrometric analysis including phospholipids (PL), sphingolipids, free cholesterol (FC), cholesteryl esters (CE) and bile acids. Our analysis of Lp-X revealed a content of 46% FC, 49% PL with 34% phosphatidylcholine (PC) as main PL component. The lipid species pattern of Lp-X showed remarkable high fractions of mono-unsaturated species including PC 32:1 and PC 34:1 and phosphatidylethanolamine (PE) 32:1 and 34:1. LDL and HDL lipid composition in the same specimens strongly reflected the lipid composition of Lp-X with increased PC 32:1, PC 34:1, PE 32:1, PE 34:1 and FC accompanied by decreased CE compared to controls. Comparison of Lp-X and biliary lipid composition clearly indicates that Lp-X does not originate from a sole release of bile lipids. Moreover, these data present evidence for increased hepatic fatty acid and PL synthesis which may represent a reaction to high hepatic FC level observed during cholestasis.

  17. SELDI-TOF mass spectrometry of High-Density Lipoprotein

    Directory of Open Access Journals (Sweden)

    Rezaee Farhad

    2007-09-01

    Full Text Available Abstract Background High-Density Lipoprotein (HDL, one of the main plasma lipoproteins, serves as a docking station for proteins involved in inflammation, coagulation, and lipid metabolism. Methods To elucidate the protein composition of HDL, we employed SELDI-TOF mass spectrometry as a potential high-throughput proteomic candidate for protein profiling of HDL. HDL derived from normolipemic individuals was captured on PS20 protein-chips using covalently bound antibodies against apo A-I or A-II. Results After optimisation, on-chip capture of HDL particles directly from plasma or from pre-purified HDL resulted in comparable fingerprints confirming specific capture of HDL. Depending on the capture antibody some differences in the fingerprint were observed. The most detailed fingerprint was observed up to 50 kDa; approximately 95 peaks were detected in the 3–50 kDa molecular mass range. Between 50 and 160 kDa, 27 more peaks were detected. Conclusion Based on these results, SELDI-TOF MS may be a suitable high-throughput candidate for HDL protein profiling and marker search. This approach may be used to i investigate the underlying mechanisms that lead to increased atherothrombotic risk and ii to investigate the atherothrombotic state of an individual.

  18. Lipoprotein (a) and cardiovascular risk factors in children and adolescents

    Science.gov (United States)

    Palmeira, Ástrid Camêlo; Leal, Adriana Amorim de F.; Ramos, Nathaly de Medeiros N.; de Alencar F., José; Simões, Mônica Oliveira da S.; Medeiros, Carla Campos M.

    2013-01-01

    OBJECTIVE: To review the relationship between lipoprotein (a) [Lp(a)] and other risk factors for cardiovascular disease (CVD) in children and adolescents. DATA SOURCES: This systematic review included studies from 2001 to 2011, a ten-year time period. Epidemiological studies with children and/or adolescents published in English, Portuguese or Spanish and fully available online were included. The searches were performed in Science Direct, PubMed/Medline, BVS (Biblioteca Virtual em Saúde) and Cochrane Library databases, using the following combination of key-words: "lipoprotein a" and "cardiovascular diseases" and "obesity". DATA SYNTHESIS: Overall, 672 studies were obtained but only seven were included. Some studies assessed the family history for CVD. In all of them, Lp(a) levels were increased in patients with family history for CVD. There was also a positive correlation between Lp(a) and LDL-cholesterol, total cholesterol, and apolipoprotein B levels, suggesting an association between Lp(a) levels and the lipid profile. CONCLUSIONS: The evidence that CVD may originate in childhood and adolescence leads to the need for investigating the risk factors during this period in order to propose earlier and possibly more effective interventions to reduce morbidity and mortality rates. PMID:24473960

  19. CMPD: cancer mutant proteome database.

    Science.gov (United States)

    Huang, Po-Jung; Lee, Chi-Ching; Tan, Bertrand Chin-Ming; Yeh, Yuan-Ming; Julie Chu, Lichieh; Chen, Ting-Wen; Chang, Kai-Ping; Lee, Cheng-Yang; Gan, Ruei-Chi; Liu, Hsuan; Tang, Petrus

    2015-01-01

    Whole-exome sequencing, which centres on the protein coding regions of disease/cancer associated genes, represents the most cost-effective method to-date for deciphering the association between genetic alterations and diseases. Large-scale whole exome/genome sequencing projects have been launched by various institutions, such as NCI, Broad Institute and TCGA, to provide a comprehensive catalogue of coding variants in diverse tissue samples and cell lines. Further functional and clinical interrogation of these sequence variations must rely on extensive cross-platforms integration of sequencing information and a proteome database that explicitly and comprehensively archives the corresponding mutated peptide sequences. While such data resource is a critical for the mass spectrometry-based proteomic analysis of exomic variants, no database is currently available for the collection of mutant protein sequences that correspond to recent large-scale genomic data. To address this issue and serve as bridge to integrate genomic and proteomics datasets, CMPD (http://cgbc.cgu.edu.tw/cmpd) collected over 2 millions genetic alterations, which not only facilitates the confirmation and examination of potential cancer biomarkers but also provides an invaluable resource for translational medicine research and opportunities to identify mutated proteins encoded by mutated genes.

  20. Study on culturing Trichodema mutants

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian-ai; WANG Wei-ming

    2004-01-01

    @@ Trichodema mutants strains T5, T0803, T1010, T1003were cultured in different conditions and media, also in the presence of fungicides at 40 mg/kg (CK or procymidone + chlorothalonil, or maneb or phosethyl-Al) . The pH values of media were 5, 6, 7 and 8 and hyphae were grown at temperatures of 15, 20, 25 and 30 ℃. After being cultured for 3, 4, 5, or 6 days, the strains were transferred at a lower temperature to sporulate (20℃) Obtained data were analyzed statistically, with the orthogonal array and ranges (R) differing dependes on the treatments (R = 40.0,42.4, 48.0, 62.8,107.0). The results indicated that the most important factor was the nature of the strain (R =107.0), while the change in temperature and time of cultivation produced the lowest effect (R =40.0). Each factor variance was significant and A3B4C2D1E3 was the optimum combined condition, in which strain T1010 grew more quickly and sporulated most.

  1. Surface-Associated Lipoproteins Link Enterococcus faecalis Virulence to Colitogenic Activity in IL-10-Deficient Mice Independent of Their Expression Levels.

    Science.gov (United States)

    Ocvirk, Soeren; Sava, Irina G; Lengfelder, Isabella; Lagkouvardos, Ilias; Steck, Natalie; Roh, Jung H; Tchaptchet, Sandrine; Bao, Yinyin; Hansen, Jonathan J; Huebner, Johannes; Carroll, Ian M; Murray, Barbara E; Sartor, R Balfour; Haller, Dirk

    2015-06-01

    The commensal Enterococcus faecalis is among the most common causes of nosocomial infections. Recent findings regarding increased abundance of enterococci in the intestinal microbiota of patients with inflammatory bowel diseases and induction of colitis in IL-10-deficient (IL-10-/-) mice put a new perspective on the contribution of E. faecalis to chronic intestinal inflammation. Based on the expression of virulence-related genes in the inflammatory milieu of IL-10-/- mice using RNA-sequencing analysis, we characterized the colitogenic role of two bacterial structures that substantially impact on E. faecalis virulence by different mechanisms: the enterococcal polysaccharide antigen and cell surface-associated lipoproteins. Germ-free wild type and IL-10-/- mice were monoassociated with E. faecalis wild type OG1RF or the respective isogenic mutants for 16 weeks. Intestinal tissue and mesenteric lymph nodes (MLN) were collected to characterize tissue pathology, loss of intestinal barrier function, bacterial adhesion to intestinal epithelium and immune cell activation. Bone marrow-derived dendritic cells (BMDC) were stimulated with bacterial lysates and E. faecalis virulence was additionally investigated in three invertebrate models. Colitogenic activity of wild type E. faecalis (OG1RF score: 7.2±1.2) in monoassociated IL-10-/- mice was partially impaired in E. faecalis lacking enterococcal polysaccharide antigen (ΔepaB score: 4.7±2.3; pfaecalis deficient for lipoproteins (Δlgt score: 2.3±2.3; pfaecalis mutants showed significantly impaired virulence in Galleria mellonella and Caenorhabditis elegans. Loss of E-cadherin in the epithelium was shown for all bacterial strains in inflamed IL-10-/- but not wild type mice. Inactivation of epaB in E. faecalis reduced microcolony and biofilm formation in vitro, altered bacterial adhesion to intestinal epithelium of germ-free Manduca sexta larvae and impaired penetration into the colonic mucus layer of IL-10-/- mice

  2. Surface-Associated Lipoproteins Link Enterococcus faecalis Virulence to Colitogenic Activity in IL-10-Deficient Mice Independent of Their Expression Levels.

    Directory of Open Access Journals (Sweden)

    Soeren Ocvirk

    2015-06-01

    Full Text Available The commensal Enterococcus faecalis is among the most common causes of nosocomial infections. Recent findings regarding increased abundance of enterococci in the intestinal microbiota of patients with inflammatory bowel diseases and induction of colitis in IL-10-deficient (IL-10-/- mice put a new perspective on the contribution of E. faecalis to chronic intestinal inflammation. Based on the expression of virulence-related genes in the inflammatory milieu of IL-10-/- mice using RNA-sequencing analysis, we characterized the colitogenic role of two bacterial structures that substantially impact on E. faecalis virulence by different mechanisms: the enterococcal polysaccharide antigen and cell surface-associated lipoproteins. Germ-free wild type and IL-10-/- mice were monoassociated with E. faecalis wild type OG1RF or the respective isogenic mutants for 16 weeks. Intestinal tissue and mesenteric lymph nodes (MLN were collected to characterize tissue pathology, loss of intestinal barrier function, bacterial adhesion to intestinal epithelium and immune cell activation. Bone marrow-derived dendritic cells (BMDC were stimulated with bacterial lysates and E. faecalis virulence was additionally investigated in three invertebrate models. Colitogenic activity of wild type E. faecalis (OG1RF score: 7.2±1.2 in monoassociated IL-10-/- mice was partially impaired in E. faecalis lacking enterococcal polysaccharide antigen (ΔepaB score: 4.7±2.3; p<0.05 and was almost completely abrogated in E. faecalis deficient for lipoproteins (Δlgt score: 2.3±2.3; p<0.0001. Consistently both E. faecalis mutants showed significantly impaired virulence in Galleria mellonella and Caenorhabditis elegans. Loss of E-cadherin in the epithelium was shown for all bacterial strains in inflamed IL-10-/- but not wild type mice. Inactivation of epaB in E. faecalis reduced microcolony and biofilm formation in vitro, altered bacterial adhesion to intestinal epithelium of germ

  3. Identification of a Novel Lipoprotein Regulator of Clostridium difficile Spore Germination.

    Directory of Open Access Journals (Sweden)

    Kelly A Fimlaid

    2015-10-01

    Full Text Available Clostridium difficile is a Gram-positive spore-forming pathogen and a leading cause of nosocomial diarrhea. C. difficile infections are transmitted when ingested spores germinate in the gastrointestinal tract and transform into vegetative cells. Germination begins when the germinant receptor CspC detects bile salts in the gut. CspC is a subtilisin-like serine pseudoprotease that activates the related CspB serine protease through an unknown mechanism. Activated CspB cleaves the pro-SleC zymogen, which allows the activated SleC cortex hydrolase to degrade the protective cortex layer. While these regulators are essential for C. difficile spores to outgrow and form toxin-secreting vegetative cells, the mechanisms controlling their function have only been partially characterized. In this study, we identify the lipoprotein GerS as a novel regulator of C. difficile spore germination using targeted mutagenesis. A gerS mutant has a severe germination defect and fails to degrade cortex even though it processes SleC at wildtype levels. Using complementation analyses, we demonstrate that GerS secretion, but not lipidation, is necessary for GerS to activate SleC. Importantly, loss of GerS attenuates the virulence of C. difficile in a hamster model of infection. Since GerS appears to be conserved exclusively in related Peptostreptococcaeace family members, our results contribute to a growing body of work indicating that C. difficile has evolved distinct mechanisms for controlling the exit from dormancy relative to B. subtilis and other spore-forming organisms.

  4. PLASMA-LIPOPROTEIN ABNORMALITIES IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

    NARCIS (Netherlands)

    DULLAART, RPF

    1995-01-01

    Lipoprotein abnormalities may well contribute to the increased risk of coronary heart disease, cerebrovascular disease and peripheral vascular disease observed in type 1 (insulin-dependent) diabetes mellitus. The spectrum of diabetes-associated changes in lipoprotein metabolism is discussed. The pla

  5. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2012-01-01

    The aim of the present study was to determine whether lipoprotein(a) [Lp(a)], considered a causal risk factor for cardiovascular disease, primarily promotes thrombosis or atherosclerosis.......The aim of the present study was to determine whether lipoprotein(a) [Lp(a)], considered a causal risk factor for cardiovascular disease, primarily promotes thrombosis or atherosclerosis....

  6. Screening for apolipoprotein E gene mutations in 4 patients with lipoprotein glomerulopathy

    Institute of Scientific and Technical Information of China (English)

    潘永利

    2006-01-01

    Objective To study the mutations of apolipoprotein E (apoE) gene in 4 Chinese lipoprotein glomerulopathy (LPG) patients and their family members, and to investigate the pathogenesis of LPG. Methods Urinalysis was performed on the family members of two patients, and they were screened for the level of serum creatinine, serum lipid and serum lipoprotein. The mutation of apoE

  7. Gene therapy for genetic lipoprotein lipase deficiency : from promise to practice

    NARCIS (Netherlands)

    Nierman, M C; Rip, J; Twisk, J; Meulenberg, J J M; Kastelein, J J P; Stroes, E S G; Kuivenhoven, J A

    2005-01-01

    Lipoprotein lipase (LPL) deficiency is a rare, hereditary disorder of lipoprotein metabolism characterised by severely increased triglyceride levels, and associated with an increased risk for pancreatitis. Since no adequate treatment modality is available for this disorder, we set out to develop an

  8. 21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-lipoprotein immuno-logical test system. 866.5580 Section 866.5580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...-lipoprotein may aid in the diagnosis of Tangier disease (a hereditary disorder of fat metabolism)....

  9. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular ...

  10. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima

    DEFF Research Database (Denmark)

    Nielsen, Lars Bo; Grønholdt, Marie-Louise; Schroeder, T V;

    1997-01-01

    The aim of this study was to compare the atherogenic potential of lipoprotein(a) [Lp(a)] and LDL by measuring the intimal clearance of these two plasma lipoproteins in the atherosclerotic intima of the human carotid artery in vivo. Autologous 131I-Lp(a) and 125I-LDL were mixed and reinjected intr...

  11. Adaptive immune response to lipoproteins of Staphylococcus aureus in healthy subjects

    NARCIS (Netherlands)

    Vu, Chi Hai; Kolata, Julia; Stentzel, Sebastian; Beyer, Anica; Salazar, Manuela Gesell; Steil, Leif; Pané-Farré, Jan; Rühmling, Vanessa; Engelmann, Susanne; Götz, Friedrich; van Dijl, Jan Maarten; Hecker, Michael; Mäder, Ulrike; Schmidt, Frank; Völker, Uwe; Bröker, Barbara M

    2016-01-01

    Staphylococcus aureus is a frequent commensal but also a dangerous pathogen, causing many forms of infection ranging from mild to life-threatening conditions. Among its virulence factors are lipoproteins, which are anchored in the bacterial cell membrane. Lipoproteins perform various functions in co

  12. Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?

    NARCIS (Netherlands)

    J.S. Rana; S.M. Boekholdt

    2010-01-01

    Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the

  13. Low normal thyroid function as a determinant of increased large very low density lipoprotein particles

    NARCIS (Netherlands)

    van Tienhoven-Wind, Lynnda; Dullaart, Robin P. F.

    2015-01-01

    Objectives: Low-normal thyroid function may relate to increases in plasma cholesterol and triglycerides, but effects on lipoprotein subfractions are largely unknown. Associations of alterations in lipoprotein metabolism and functionality with low-normal thyroid function could be more pronounced in T

  14. Nanoporous carbon sorbent for molecular-sieve chromatography of lipoprotein complex

    Science.gov (United States)

    Kerimkulova, A. R.; Mansurova, B. B.; Gil'manov, M. K.; Mansurov, Z. A.

    2012-06-01

    The physicochemical characteristics of carbon sorbents are investigated. Electron microscopy data for the sorbent and separated lipoprotein complex are presented. It is found that the obtained carbon sorbent possess high porosity. Nanoporous carbon sorbents for the chromatography of molecular-sieve markers are obtained and tested. The applicability of nanoporous carbon sorbents for separation of lipoprotein complexes (LPC) is investigated.

  15. Application of directly coupled HPLC MMR to separation and characterization of lipoproteins from human serum

    DEFF Research Database (Denmark)

    Daykin, C. A.; Corcoran, O.; Hansen, S. H.;

    2001-01-01

    Disorders in lipoprotein metabolism are critical in the etiology of several disease states such as coronary heart disease and atherosclerosis, Thus, there is considerable interest in the development of novel methods for the analysis of lipoprotein complexes. We report here a simple chromatographi...

  16. Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum.

    Science.gov (United States)

    Hellman, J; Loiselle, P M; Tehan, M M; Allaire, J E; Boyle, L A; Kurnick, J T; Andrews, D M; Sik Kim, K; Warren, H S

    2000-05-01

    Complexes containing lipopolysaccharide (LPS) and three outer membrane proteins (OMPs) are released by gram-negative bacteria incubated in human serum and into the circulation in an experimental model of sepsis. The same OMPs are bound by immunoglobulin G (IgG) in the cross-protective antiserum raised to Escherichia coli J5 (anti-J5 IgG). This study was performed to identify the three OMPs. The 35-kDa OMP was identified as outer membrane protein A (OmpA) by immunoblotting studies using OmpA-deficient bacteria and recombinant OmpA protein. The 18-kDa OMP was identified as peptidoglycan-associated lipoprotein (PAL) based on peptide sequences from the purified protein and immunoblotting studies using PAL-deficient bacteria. The 5- to 9-kDa OMP was identified as murein lipoprotein (MLP) based on immunoblotting studies using MLP-deficient bacteria. The studies identify the OMPs released into human serum and into the circulation in an experimental model of sepsis as OmpA, PAL, and MLP.

  17. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus

    2008-01-01

    To investigate the role of apoM in high density lipoprotein (HDL) metabolism and atherogenesis, we generated human apoM transgenic (apoM-Tg) and apoM-deficient (apoM(-/-)) mice. Plasma apoM was predominantly associated with 10-12-nm alpha-migrating HDL particles. Human apoM overexpression (11-fold...... of alpha- to pre-alpha-migrating HDL was delayed in apoM-Tg mice. Moreover, lecithin: cholesterol acyltransferase-independent generation of pre-beta-migrating apoA-I-containing particles in plasma was increased in apoM-Tg mice (4.2 +/- 1.1%, p = 0.06) and decreased in apoM(-/-) mice (0.5 +/- 0.3%, p = 0.......03) versus controls (1.8 +/- 0.05%). In the setting of low density lipoprotein receptor deficiency, apoM-Tg mice with approximately 2-fold increased plasma apoM concentrations developed smaller atherosclerotic lesions than controls. The effect of apoM on atherosclerosis may be facilitated by enzymatic...

  18. Identification and quantification of regioisomeric cholesteryl linoleate hydroperoxides in oxidized human low density lipoprotein and high density lipoprotein.

    Science.gov (United States)

    Kenar, J A; Havrilla, C M; Porter, N A; Guyton, J R; Brown, S A; Klemp, K F; Selinger, E

    1996-06-01

    Oxidation of human LDL is implicated as an initiator of atherosclerosis. Isolated low density lipoprotein (LDL) and high density lipoprotein (HDL2) were exposed to aqueous radicals generated from the thermolabile azo compound 2,2'-azobis(2-amidinopropane) dihydrochloride. The primary nonpolar lipid products formed from the autoxidation of LDL and HDL were the regioisomeric cholesteryl linoleate hydroperoxides. In LDL oxidations, 9- and 13-hydroperoxides with trans,cis conjugated diene were formed as the major oxidation products if endogenous alpha-tocopheral was present in the LDL. After extended oxidation of LDL, at the time when endogenous alpha-tocopherol was consumed, the two trans,cis conjugated diene hydroperoxides began to disappear and the 9- and 13-hydroperoxides with trans,trans conjugated diene appeared. At very long oxidation times, none of the primary products, the conjugated diene hydroperoxides, were present. In HDL2, which has only very low levels of antioxidants, both the 9- and 13-hydroperoxides with trans,cis conjugated diene and the 9- and 13-hydroperoxides with trans,trans conjugated diene were formed at early stages of oxidation. The corresponding alcohols were also formed in the HDL2 oxidations. A mechanistic hypothesis consistent with these observations is presented.

  19. Effect of omega-3 fatty acids on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects

    Science.gov (United States)

    Background: Oxylipins mediate many physiological processes, including inflammation and vascular function. Generally considered local and transient, we suggest their presence in lipoproteins indicates they also mediate the effects lipoproteins have on inflammation and vascular biology. To support th...

  20. Amphotericin B toxicity as related to the formation of oxidatively modified low-density lipoproteins.

    Science.gov (United States)

    Barwicz, J; Dumont, I; Ouellet, C; Gruda, I

    1998-01-01

    The effect of amphotericin B on the oxidation and degradation of low- and high-density lipoproteins was investigated by UV-vis spectroscopy, electron microscopy, electrophoresis, and size-exclusion chromatography. Two formulations of the drug were used: the commercial Fungizone and a new, less toxic, liposomal formulation, AmBisome. It was shown that Fungizone strongly enhanced the oxidative deformation of low-density lipoprotein structure while AmBisome did not bind to this lipoprotein fraction and did not affect its oxidation. It was shown that amphotericin B contained in Fungizone extracted cholesterol from low-density lipoproteins which sensitized them to oxidation. Both formulations of amphotericin B studied here did not bind to high-density lipoprotein and did not affect the process of its oxidation.

  1. Roles of lipoprotein receptors in the entry of hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Jingya; Lyu; Hitomi; Imachi; Kensaku; Fukunaga; Takuo; Yoshimoto; Huanxiang; Zhang; Koji; Murao

    2015-01-01

    Infection by hepatitis C virus(HCV), a plus-stranded RNA virus that can cause cirrhosis and hepatocellular carcinoma, is one of the major health problems in the world. HCV infection is considered as a multistep complex process and correlated with abnormal metabolism of lipoprotein. In addition, virus attacks hepatocytes by the initial attaching viral envelop glycoprotein E1/E2 to receptors of lipoproteins on host cells. With the development of HCV model system, mechanisms of HCV cell entry through lipoprotein uptake and its receptor have been extensively studied in detail. Here we summarize recent knowledge about the role of lipoprotein receptors, scavenger receptor class B type Ⅰ and low-density lipoprotein receptor in the entry of HCV, providing a foundation of novel targeting therapeutic tools against HCV infection.

  2. NMR and interval PLS as reliable methods for determination of cholesterol in rodent lipoprotein fractions

    DEFF Research Database (Denmark)

    Kristensen, Mette; Savorani, Francesco; Ravn-Haren, Gitte

    2010-01-01

    Risk of cardiovascular disease is related to cholesterol distribution in different lipoprotein fractions. Lipoproteins in rodent model studies can only reliably be measured by time- and plasma-consuming fractionation. An alternative method to measure cholesterol distribution in the lipoprotein...... data and the NMR spectra, an interval partial least-square (iPLS) regression model to predict the amount of cholesterol in the different lipoprotein fractions was developed. The relative errors of the prediction models were between 12 and 33% and had correlation coefficients (r) between 0.96 and 0.......84. The models were tested with an independent test set giving prediction errors between 19 and 46% and r between 0.96 and 0.76. Prediction of High, Low and Very Low Density Lipoprotein (HDL, LDL and VLDL) and total cholesterol was conducted in a study where rats had been supplemented with two doses of air...

  3. Stability of serum high-density lipoprotein-microRNAs for preanalytical conditions.

    Science.gov (United States)

    Ishikawa, Hiroaki; Yamada, Hiroya; Taromaru, Nao; Kondo, Kanako; Nagura, Ayuri; Yamazaki, Mirai; Ando, Yoshitaka; Munetsuna, Eiji; Suzuki, Koji; Ohashi, Koji; Teradaira, Ryoji

    2017-01-01

    Background Recently, several studies have shown that microRNAs are present in high-density lipoprotein, and high-density lipoprotein-microRNA may be a promising disease biomarker. We investigated the stability of high-density lipoprotein-microRNAs in different storage conditions as this is an important issue for its application to the field of clinical research. Methods microRNAs were extracted from the high-density lipoprotein fraction that was purified from the serum. miR-135 a and miR-223, which are known to be present in high-density lipoprotein, were quantified by quantitative real-time PCR. The influence of preanalytical parameters on the analysis of high-density lipoprotein-miRNAs was examined by the effect of RNase, storage conditions, and freezing and thawing. Results The concentrations of microRNA in high-density lipoprotein were not altered by RNase A treatment (0-100 U/mL). No significant change in these microRNAs was observed after storing serum at room temperature or 4℃ for 0-24 h, and there was a similar result in the cryopreservation for up to two weeks. Also, high-density lipoprotein-microRNAs were stable for, at least, up to five freeze-thaw cycles. Conclusions These results demonstrated that high-density lipoprotein-microRNAs are relatively resistant to various storage conditions. This study provides new and important information on the stability of high-density lipoprotein-microRNAs.

  4. Characterization and Purification of Polydisperse Reconstituted Lipoproteins and Nanolipoprotein Particles

    Directory of Open Access Journals (Sweden)

    Paul D. Hoeprich

    2009-07-01

    Full Text Available Heterogeneity is a fact that plagues the characterization and application of many self-assembled biological constructs. The importance of obtaining particle homogeneity in biological assemblies is a critical goal, as bulk analysis tools often require identical species for reliable interpretation of the results—indeed, important tools of analysis such as x-ray diffraction typically require over 90% purity for effectiveness. This issue bears particular importance in the case of lipoproteins. Lipid-binding proteins known as apolipoproteins can self assemble with liposomes to form reconstituted high density lipoproteins (rHDLs or nanolipoprotein particles (NLPs when used for biotechnology applications such as the solubilization of membrane proteins. Typically, the apolipoprotein and phospholipids reactants are self assembled and even with careful assembly protocols the product often contains heterogeneous particles. In fact, size polydispersity in rHDLs and NLPs published in the literature are frequently observed, which may confound the accurate use of analytical methods. In this article, we demonstrate a procedure for producing a pure, monodisperse NLP subpopulation from a polydisperse self-assembly using size exclusion chromatography (SEC coupled with high resolution particle imaging by atomic force microscopy (AFM. In addition, NLPs have been shown to self assemble both in the presence and absence of detergents such as cholate, yet the effects of cholate on NLP polydispersity and separation has not been systematically examined. Therefore, we examined the separation properties of NLPs assembled in both the absence and presence of cholate using SEC and native gel electrophoresis. From this analysis, NLPs prepared with and without cholate showed particles with well defined diameters spanning a similar size range. However, cholate was shown to have a dramatic affect on NLP separation by SEC and native gel electrophoresis. Furthermore, under

  5. Zn2+ Uptake in Streptococcus pyogenes: Characterization of adcA and lmb Null Mutants.

    Science.gov (United States)

    Tedde, Vittorio; Rosini, Roberto; Galeotti, Cesira L

    2016-01-01

    An effective regulation of metal ion homeostasis is essential for the growth of microorganisms in any environment and in pathogenic bacteria is strongly associated with their ability to invade and colonise their hosts. To gain a better insight into zinc acquisition in Group A Streptococcus (GAS) we characterized null deletion mutants of the adcA and lmb genes of Streptococcus pyogenes strain MGAS5005 encoding the orthologues of AdcA and AdcAII, the two surface lipoproteins with partly redundant roles in zinc homeostasis in Streptococcus pneumoniae. Null adcA and lmb mutants were analysed for their capability to grow in zinc-depleted conditions and were found to be more susceptible to zinc starvation, a phenotype that could be rescued by the addition of Zn2+ ions to the growth medium. Expression of AdcA, Lmb and HtpA, the polyhistidine triad protein encoded by the gene adjacent to lmb, during growth under conditions of limited zinc availability was examined by Western blot analysis in wild type and null mutant strains. In the wild type strain, AdcA was always present with little variation in expression levels between conditions of excess or limited zinc availability. In contrast, Lmb and HtpA were expressed at detectable levels only during growth in the presence of low zinc concentrations or in the null adcA mutant, when expression of lmb is required to compensate for the lack of adcA expression. In the latter case, Lmb and HtpA were overexpressed by several fold, thus indicating that also in GAS AdcA is a zinc-specific importer and, although it shares this function with Lmb, the two substrate-binding proteins do not show fully overlapping roles in zinc homeostasis.

  6. Low density lipoprotein receptor-related protein-2/megalin is expressed in oligodendrocytes in the mouse spinal cord white matter

    DEFF Research Database (Denmark)

    Wicher, Grzegorz; Larsson, Mårten; Svenningsen, Åsa Fex;

    2006-01-01

    Lipoprotein receptor-related protein-2 (LRP2)/megalin is a member of the low density lipoprotein receptor (LDLR) family, and is essential in absorptive epithelia for endocytosis of lipoproteins, low molecular weight proteins, cholesterol and vitamins, as well as in cellular signaling. Previous...

  7. Bio F1B hamster: a unique animal model with reduced lipoprotein lipase activity to investigate nutrient mediated regulation of lipoprotein metabolism

    Directory of Open Access Journals (Sweden)

    Cornish Marion L

    2007-12-01

    Full Text Available Abstract Background Bio F1B hamster is an inbred hybrid strain that is highly susceptible to diet-induced atherosclerosis. We previously reported that feeding a high fat fish oil diet to Bio F1B hamster caused severe hyperlipidaemia. In this study we compared the effects of various diets in the Bio F1B hamster and the Golden Syrian hamster, which is an outbred hamster strain to investigate whether genetic background plays an important role in dietary fat mediated regulation of lipoprotein metabolism. We further investigated the mechanisms behind diet-induced hyperlipidaemia in F1B hamster. Methods The Bio F1B and Golden Syrian hamsters, 8 weeks old, were fed high fat diets rich in either monounsaturated fatty acids, an n-6: n-3 ratio of 5 or a fish oil diet for 4 weeks. Animals were fasted overnight and blood and tissue samples were collected. Plasma was fractionated into various lipoprotein fractions and assayed for triacylglycerol and cholesterol concentrations. Plasma lipoprotein lipase activity was measured using radioisotope method. Microsomal triglyceride transfer protein activity was measured in the liver and intestine. Plasma apolipoproteinB48, -B100 and apolipoprotein E was measured using Western blots. Two-way ANOVA was used to determine the effect of diet type and animal strain. Results The fish oil fed F1B hamsters showed milky plasma after a 14-hour fast. Fish oil feeding caused accumulation of apolipoproteinB48 containing lipoprotein particles suggesting hindrance of triglyceride-rich lipoprotein clearance. There was no significant effect of diet or strain on hepatic or intestinal microsomal triglyceride transfer protein activity indicating that hyperlipidaemia is not due to an increase in the assembly or secretion of lipoprotein particles. F1B hamsters showed significantly reduced levels of lipoprotein lipase activity, which was inhibited by fish oil feeding. Conclusion Evidence is presented for the first time that alterations in

  8. Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution.

    Science.gov (United States)

    Sánchez-Quesada, José L; Vinagre, Irene; de Juan-Franco, Elena; Sánchez-Hernández, Juan; Blanco-Vaca, Francisco; Ordóñez-Llanos, Jordi; Pérez, Antonio

    2012-07-01

    The aim of this study was to determine the effect of intensified hypoglycemic therapy in patients with type 2 diabetes mellitus on the distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity between high-density lipoprotein and low-density lipoprotein (LDL) and its relation with the lipid profile and other qualitative properties of LDL. Forty-two patients with type 2 diabetes on the basis of poor glycemic control and normal or near normal LDL cholesterol were recruited. Lifestyle counseling and pharmacologic hypoglycemic therapy were intensified to improve glycemic control, but lipid-lowering therapy was unchanged. At 4 ± 2 months, glycosylated hemoglobin had decreased by a mean of 2.1%, but the only effect on the lipid profile were statistically significant decreases in nonesterified fatty acids and apolipoprotein B concentration. LDL size increased and the proportion of electronegative LDL decreased significantly. In parallel, total Lp-PLA2 activity decreased significantly, promoting a redistribution of Lp-PLA2 activity toward a higher proportion in high-density lipoprotein. Improvements in glycemic control led to more marked changes in Lp-PLA2 activity and distribution in patients with diabetes who had not received previous lipid-lowering therapy. In conclusion, optimizing glycemic control in patients with type 2 diabetes promotes atheroprotective changes, including larger LDL size, decreased electronegative LDL, and a higher proportion of Lp-PLA2 activity in high-density lipoprotein.

  9. Interaction of variable bacterial outer membrane lipoproteins with brain endothelium.

    Directory of Open Access Journals (Sweden)

    Gaurav Gandhi

    Full Text Available BACKGROUND: Previously we reported that the variable outer membrane lipoprotein Vsp1 from the relapsing fever spirochete Borrelia turicatae disseminates from blood to brain better than the closely related Vsp2 [1]. Here we studied the interaction between Vsp1 and Vsp2 with brain endothelium in more detail. METHODOLOGY/PRINCIPAL FINDINGS: We compared Vsp1 to Vsp2 using human brain microvascular endothelial cell (HBMEC association assays with aminoacid radiolabeled Vsp-expressing clones of recombinant Borrelia burgdorferi and lanthanide-labeled purified lipidated Vsp1 (LVsp1 and Vsp2 (LVsp2 and inoculations of the lanthanide-labeled proteins into mice. The results showed that heterologous expression of LVsp1 or LVsp2 in B. burgdorferi increased its association with HBMEC to a similar degree. Purified lanthanide-labeled lipidated Vsp1 (LVsp1 and LVsp2 by themselves were capable of associating with HBMEC. The association of LVsp1 with brain endothelium was time-dependent, saturable, and required the lipidation. The association of Vsp1 with HBMEC was inhibited by incubation at lower temperature or with excess unlabeled LVsp1 or LVsp2 but not with excess rVsp1 or mouse albumin or an anti Vsp1 monoclonal antibody. The association of LVsp2 with HBMEC and its movement from blood to brain parenchyma significantly increased in the presence of LVsp1. CONCLUSIONS/SIGNIFICANCE: Variable bacterial outer membrane lipoproteins interact with brain endothelium differently; the lipidation and variable features at the protein dome region are key modulators of this interaction.

  10. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  11. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1-Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1-Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...mutations found in breast cancer using both structural and cell based assays. We have now have evidence for the effects of the most recurrent

  12. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    Introduction Approximately 70% of ER+ breast cancers harbor expression of the estrogen receptor and are dependent upon its activity for various aspects of the...resistance to current FDA approved ER antagonists, but that more potent and selective estrogen receptor antagonists will be sufficiently active to...antagonists and their potency against ER mutants both in vitro and in vivo . Targeting ESR1-Mutant Breast Cancer W81XWH-14-1-0359 9 4. Impact A) Impact

  13. Thermal transitions in the low-density lipoprotein and lipids of the egg yolk of hens.

    Science.gov (United States)

    Smith, M B; Back, J F

    1975-05-22

    1. Differential sanning calorimetry and light-scattering have been used to investigate temperature-dependent transitions in low-density lipoprotein and in lipids from hens' egg yolk. Yolks of different fatty acid composition were obtained by varying the dietary lipid and by adding methyl sterculate to the hen's diet. 2. Lipoprotein solutions in 50 percent glycerol/water gave characteristic melting curves between -25 degrees C and 50 degrees C, and on cooling showed increases in light-scattering between 10 degrees C and -20 degrees C. The temperatures at which major changes occurred depended on the proportions of saturated and unsaturated fatty acids. 3. The thermal transitions in the intact lipoprotein in glycerol solution were reversible, but with marked hysteresis. Lipid extracted from the lipoprotein did not show temperature hystersis but the transition heats and melting curves similar to those of the intact lipoprotein. The results support the hypothesis of a "lipid-core" structure for low-density lipoproteins. 4. Scanning calorimetry of egg-yolk lecithins indicated a strong dependence of transition temperature on water content in the rane 3 percent-20 percent water. A rise in the mid-temperature of the liquid-crystalline to gel transition as the water content is lowered on freezing may be the primary event in the irreversible gelation of egg yolk and aggregation of lipoprotein.

  14. Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood.

    Science.gov (United States)

    Aynaci, F M; Orhan, F; Orem, A; Yildirmis, S; Gedik, Y

    2001-05-01

    Antiepileptic drugs may alter plasma lipid status in epileptic patients. We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on plasma levels of lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B in 22 epileptic children. The children were separated as group 1, seven children, mean age 1.6+/-0.2 years, treated with phenobarbital, 5 mg/kg/day, twice daily; group 2, seven children, mean age 9.8+/-1.2 years, treated with carbamazepine, 20 mg/kg/day, twice daily; and group 3, eight children, mean age 6.8+/-0.6 years, treated with valproate, 20 mg/kg/day, twice daily. Plasma lipoprotein (a) and other lipid levels were studied before (pretreatment) and at 3 and 6 months of treatment. Friedman two-way analysis of variance and Wilcoxon's signed-rank test were used for statistical analysis, and the results were expressed as the mean and standard error of the mean. The mean age of children in group 1 was significantly low, compared with groups 2 and, 3 (P < .001). The mean pretreatment lipid levels between the groups were not significant. The increase in lipoprotein (a) at 3 and 6 months and high-density lipoprotein cholesterol at 6 months was statistically significant in group 1 (P < .025). We suggest a careful monitoring of plasma levels of lipoprotein (a) and other lipids in epileptic children treated with antiepileptic drugs.

  15. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes.

    Science.gov (United States)

    Sonmez, Fatma Mujgan; Demir, Ercan; Orem, Asim; Yildirmis, Sermet; Orhan, Fazil; Aslan, Adnan; Topbas, Murat

    2006-01-01

    We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

  16. Brucella ovis PA mutants for outer membrane proteins Omp10, Omp19, SP41, and BepC are not altered in their virulence and outer membrane properties.

    Science.gov (United States)

    Sidhu-Muñoz, Rebeca S; Sancho, Pilar; Vizcaíno, Nieves

    2016-04-15

    Mutants in several genes have been obtained on the genetic background of virulent rough (lacking O-polysaccharide) Brucella ovis PA. The target genes encode outer membrane proteins previously associated with the virulence of smooth (bearing O-polysaccharide chains in the lipopolysaccharide) Brucella strains. Multiple attempts to delete omp16, coding for a homologue to peptidoglycan-associated lipoproteins, were unsuccessful, which suggests that Omp16 is probably essential for in vitro survival of B. ovis PA. Single deletion of omp10 or omp19-that encode two other outer membrane lipoproteins--was achieved, but the simultaneous removal of both genes failed, suggesting an essential complementary function between both proteins. Two other deletion mutants, defective in the Tol-C-homologue BepC or in the SP41 adhesin, were also obtained. Surprisingly when compared to previous results obtained with smooth Brucella, none of the B. ovis mutants showed attenuation in the virulence, either in the mouse model or in cellular models of professional and non-professional phagocytes. Additionally, and in contrast to the observations reported with smooth Brucella strains, several properties related to the outer membrane remained almost unaltered. These results evidence new distinctive traits between naturally rough B. ovis and smooth brucellae.

  17. High density lipoprotein level is negatively associated with the increase of oxidized low density lipoprotein lipids after a fatty meal.

    Science.gov (United States)

    Tiainen, Sanna; Ahotupa, Markku; Ylinen, Petteri; Vasankari, Tommi

    2014-12-01

    Recent reports show that a fatty meal can substantially increase the concentration of oxidized lipids in low density lipoprotein (LDL). Knowing the LDL-specific antioxidant effects of high density lipoprotein (HDL), we aimed to investigate whether HDL can modify the postprandial oxidative stress after a fatty meal. Subjects of the study (n = 71) consumed a test meal (a standard hamburger meal) rich in lipid peroxides, and blood samples were taken before, 120, 240, and 360 min after the meal. The study subjects were divided into four subgroups according to the pre-meal HDL cholesterol value (HDL subgroup 1, 0.66-0.91; subgroup 2, 0.93-1.13; subgroup 3, 1.16-1.35; subgroup 4, 1.40-2.65 mmol/L). The test meal induced a marked postprandial increase in the concentration of oxidized LDL lipids in all four subgroups. The pre-meal HDL level was associated with the extent of the postprandial rise in oxidized LDL lipids. From baseline to 6 h after the meal, the concentration of ox-LDL increased by 48, 31, 24, and 16% in the HDL subgroup 1, 2, 3, and 4, respectively, and the increase was higher in subgroup 1 compared to subgroup 3 (p = 0.028) and subgroup 4 (p = 0.0081), respectively. The pre-meal HDL correlated with both the amount and the rate of increase of oxidized LDL lipids. Results of the present study show that HDL is associated with the postprandial appearance of lipid peroxides in LDL. It is therefore likely that the sequestration and transport of atherogenic lipid peroxides is another significant mechanism contributing to cardioprotection by HDL.

  18. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    Energy Technology Data Exchange (ETDEWEB)

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  19. Measurement of cholesterol and other lipoprotein constituents in the clinical laboratory.

    Science.gov (United States)

    Warnick, G R

    2000-04-01

    Measurements of lipids and lipoproteins in the clinical laboratory have become increasingly important because of their predictive association with cardiovascular diseases, especially coronary artery disease. The US National Institutes of Health-sponsored National Cholesterol Education Program and counterparts in other countries have developed national consensus guidelines for diagnosis and treatment of coronary artery disease which provide risk cut-points and define use of the lipid/lipoprotein analytes in case finding and therapy. Total and low density lipoprotein cholesterol and triglycerides are measured as positive risk factors and high density lipoprotein cholesterol as an inverse risk factor for coronary artery disease. A National Cholesterol Education Program-sponsored expert laboratory panel has developed guidelines for measurements with requisite analytical performance targets for total error and corresponding precision and bias. The US Centers for Disease Control and Prevention have established reference methods for total and high density lipoprotein cholesterol and for triglycerides, with a method for low density lipoprotein cholesterol in development. Standardization programs for research laboratories and a Cholesterol Reference Method Laboratory Network for diagnostic manufacturers and clinical laboratories provide reliable access and documentation of traceability to accepted reference methods. Methods for the lipid/lipoprotein analytes have improved dramatically in recent years and, coupled with improved chemistry analyzer systems and more attention to standardization by manufacturers, offer considerable improvement in analytical performance. Fully automated homogeneous assays for high density lipoprotein cholesterol and newer similar assays for low-density lipoprotein cholesterol have potential for better precision as well as more convenient and cost-effective measurements. Attention to pre-analytical sources of variation is also important in making

  20. Sexual differences in lipoprotein composition in a family with dyslipidemic hypertension with premature atheroschlerosis: deficiency of high-density lipoprotein-L and high-density lipoprotein-M "apolipoprotein-I alone" particle.

    Science.gov (United States)

    Hughes, T A; Moore, M A; Joyce, M; Go, R C; Segrest, J P; Blackwell, T

    1992-01-01

    This article describes a family with a high incidence of premature atherosclerosis and primary hypertriglyceridemia in the women. The lipoprotein composition of this family was investigated with a new methodology that combines gradient ultracentrifugation to isolate lipoprotein subfractions with high-performance liquid chromatography to quantitate apolipoproteins. The major lipoprotein abnormalities that were identified in the hyperlipidemic women in this family were (1) an increased mass of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) with triglyceriderich VLDL but normal IDL composition; (2) triglyceride-rich low-density lipoprotein (LDL) with normal cholesterol and apolipoprotein B concentrations; (3) a relatively normal total mass of high-density lipoprotein (HDL)-L and HDL-M but with a reduction in the apolipoprotein A-I/A-II ratio and a decrease in the cholesterol to triglyceride ratio; (4) an elevation of HDL-D apolipoprotein A-I. The reduction in the apolipoprotein A-I/A-II ratio was also seen in the hyperlipidemic men and in most of nonhyperlipidemic family members and was the most common lipoprotein abnormality that was identified in this family (9 of 11 family members who were not on lipid-lowering medications were affected). The hypertriglyceridemic women appeared to have an increase in the "A-I + A-II" HDL particles in all subfractions and an increase in the "A-I alone" particles in HDL-D. These increases provided the apparently normal total mass of HDL that was observed in these women. These increases in HDL were not seen in the hypertriglyceridemic men. We conclude that a deficiency of the "A-I alone" particle in HDL-L and HDL-M may contribute to the premature atherosclerosis that was seen in this family and that it appears to precede the appearance of hypertriglyceridemia. The increase in the "A-I + A-II" HDL particles did not appear to provide the same protection as would be expected from "A-I alone" HDL.

  1. High-density lipoprotein cholesterol on a roller coaster: where will the ride end?

    Science.gov (United States)

    Kronenberg, Florian

    2016-04-01

    Bowe et al. report an association between low high-density lipoprotein cholesterol concentrations and various incident chronic kidney disease end points in a cohort of almost 2 million US veterans followed for 9 years. These impressive data should be a starting point for further investigations including genetic epidemiologic investigations as well as post hoc analyses of interventional trials that target high-density lipoprotein cholesterol and, finally, studies that focus on the functionality of high-density lipoprotein particles.

  2. [Lipoproteins HDL and coronary artery disease: a molecular mechanism of fibrate].

    Science.gov (United States)

    Kaletha, Krystian; Chodorowski, Zygmunt; Anand, Izabela Sein; Rybakowska, Iwona; Nagel-Starczynowska, Gabriela

    2003-01-01

    The importance of dyslipidemia in the development of cardiovascular disease is now recognized as a central factor of equal, if not greater significance than any other risk factor. Although correction of high level of low-density lipoproteins (LDL) has been regarded now as the main goal of therapy, it has now been reaffirmed that the contribution of low level of high-density lipoproteins (HDL) to the risk of ischaemic heart disease should also be considered. In the therapy of dislipidemias with hipertriglyceridemia and decreased level of HDL lipoprotein fibrates play an especially important role. In the article the molecular mechanism of fibrates action is presented.

  3. Recurrent Embolic Strokes of Undetermined Source in a Patient with Extreme Lipoprotein(a Levels

    Directory of Open Access Journals (Sweden)

    Zachary Bulwa

    2016-08-01

    Full Text Available Lipoprotein(a is a plasma lipoprotein and known cardiovascular risk factor most recently implicated in the development of high-risk carotid atherosclerotic plaques without significant carotid stenosis. We present a case of a young African-American female with recurrent embolic strokes of undetermined source. After our thorough investigation we identified the link between a small, irregular plaque in the right internal carotid artery and an extremely elevated plasma level of lipoprotein(a as the source of her embolic strokes.

  4. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Benn, Marianne; Tybjaerg-Hansen, Anne;

    2008-01-01

    of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates.......Elevated lipoprotein(a) levels are associated with myocardial infarction (MI) in some but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples, no correction for regression dilution bias, and lack...

  5. Obstructive jaundice leads to accumulation of oxidized low density lipoprotein in human liver tissue

    Institute of Scientific and Technical Information of China (English)

    Mustafa Comert; Yucel Ustundag; Ishak Ozel Tekin; Banu Dogan Gun; Figen Barut

    2006-01-01

    Oxidized low density lipoprotein (ox-LDL) molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflammatory mechanisms in association with oxidant stress. We have reported the accumulation of ox-LDL in Balb/c mice liver after bile duct ligation previously. Here, we investigated this finding in human beings with obstructive jaundice.Our study demonstrates that obstructive jaundice results in tremendous accumulation of ox-LDL in the liver tissue of patients.

  6. Crystal structures of bacterial lipoprotein localization factors, LolA and LolB

    OpenAIRE

    Takeda, Kazuki; Miyatake, Hideyuki; Yokota, Naoko; Matsuyama, Shin-ichi; Tokuda, Hajime; Miki, Kunio

    2003-01-01

    Lipoproteins having a lipid-modified cysteine at the N-terminus are localized on either the inner or the outer membrane of Escherichia coli depending on the residue at position 2. Five Lol proteins involved in the sorting and membrane localization of lipoprotein are highly conserved in Gram-negative bacteria. We determined the crystal structures of a periplasmic chaperone, LolA, and an outer membrane lipoprotein receptor, LolB. Despite their dissimilar amino acid sequences, the structures of ...

  7. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre;

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop......Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high......-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic...... studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated...

  8. Homozygosity for two point mutations in the lipoprotein lipase (LPL) gene in a patient with familial LPL deficiency: LPL(Asp9-->Asn, Tyr262-->His).

    Science.gov (United States)

    Rouis, M; Lohse, P; Dugi, K A; Lohse, P; Beg, O U; Ronan, R; Talley, G D; Brunzell, J D; Santamarina-Fojo, S

    1996-03-01

    Familial lipoprotein lipase (LPL) deficiency is an inherited disorder of lipoprotein metabolism characterized by hypertriglyceridemia and recurrent episodes of abdominal pain and pancreatitis. We have studied the genetic basis of LPL deficiency in a 62-year-old black male with undetectable pre- and post-heparin plasma LPL mass and activity, DNA sequence analysis of the patient's LPL cDNA and gene as well as digestion with Bcl I and Asu I revealed that the proband is a homozygote for two separate gene defects. One mutation changed a G to an A, resulting in the conversion of amino acid 9 of the mature protein, aspartic acid (GAC), to asparagine (AAC). The second substitution, a C for a T, replaced tyrosine (TAC) at residue 262 with histidine (CAC). Northern blot analysis of monocyte-derived macrophage RNA demonstrated the presence of LPL mRNA of approximately normal size and quantity when compared to control. Expression of both mutations separately (pCMV-9 and pCMV-262) or in combination (pCMV-9+262) in human embryonal kidney-293 cells demonstrated that LPL-9 had approximately 80% the specific activity of wild type LPL, but LPL-262 and LPL-9+262 had no enzymic activity, thus establishing the functional significance of the LPL-262 defect. Despite an absolute deficiency of LPL mass and activity demonstrated by analysis of patient post-heparin plasma, in vitro expression of both LPL mutants was normal, suggesting that the absence of LPL in patient post-heparin plasma was a result of altered in vivo processing. Analysis of the heparin binding properties of the mutant enzymes by heparin-Sepharose affinity chromatography indicated that most of the LPL-262 mass was present in an inactive peak, which like the normal LPL monomer, eluted at 0.8 M NaCl. Thus, the Tyr262 --> His mutation may alter the stability of the LPL dimer, leading to the formation of inactive LPL-262 monomer which exhibits reduced heparin affinity. Based on these results, we propose that, in vivo, enhanced

  9. [Lipoprotein (a)--a mysterious factor in atherogenesis].

    Science.gov (United States)

    Jelaković, Bojan; Laganović, Mario; Kuzmanić, Dusko

    2002-01-01

    Etiopathogenesis of arterial hypertension and coronary disease involves interaction of numerous exogenous factors which determine the clinical course and therapeutic response in genetically predisposed individuals. The role of numerous cardiovascular risk factors has been reevaluated during the past few years, yet some unresolved issues and gaps still remain. One of the still insufficiently studied factors is lipoprotein (a) [Lp (a)] which belongs to a subclass of LDL lipoproteins. Its important component is apolipoprotein (a) which is structurally similar to plasminogen. This characteristic can be followed through evolution and is probably crucial for its physiologic but also pathophysiologic role. Actually, through its competition with plasminogen, Lp (a) interferes with the process of fibrinolysis and may contribute to tissue healing and restoration but also support and accelerate atherothrombotic process. Lp (a) concentration is stable and genetically determined in an individual and the indication that persons with elevated levels are permanently exposed to increased risk is supported by the data on twofold incidence of myocardial infarction in mothers of children with highest Lp (a) concentrations. Apart from competing with plasminogen via apolipoprotein (a), Lp (a) increases the activity of inhibitors of plasminogen-I activator and reduces the activity of transforming growth factor-beta. This results both in the absence of fibrinolysis and promotion of migration and proliferation of media smooth muscle cells, which are important in the onset of atherosclerotic process. Lp (a) binds to elastin via apolipoprotein B, resulting in oxidation and facilitated entry into macrophages and their transition into the so-called foam cells, also an important sign of early atherosclerosis. Although many pathophysiologic processes by which Lp (a) contributes to atherosclerosis have also been confirmed by animal experiments as well as by the presence of histologic evidence

  10. Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy

    Directory of Open Access Journals (Sweden)

    Orlando Robert A

    2007-10-01

    Full Text Available Abstract Background A major portion of available fatty acids for adipocyte uptake is derived from lipoprotein lipase (LPL-mediated hydrolysis of circulating lipoprotein particles. In vivo studies aimed at identifying the precise role of adipocyte-derived LPL in fat storage function of adipose tissue have been unable to provide conclusive evidence due to compensatory mechanisms that activate endogenous fatty acid synthesis. To address this gap in knowledge, we have measured the effect of reducing adipocyte LPL expression on intracellular lipid accumulation using a well-established cultured model of adipocyte differentiation. Methods siRNA specific for mouse LPL was transfected into 3T3-L1 adipocytes. Expression of LPL was measured by quantitative real-time PCR and cell surface-associated LPL enzymatic activity was measured by colorimetric detection following substrate (p-nitrophenyl butyrate hydrolysis. Apolipoprotein CII and CIII expression ratios were also measured by qRT-PCR. Intracellular lipid accumulation was quantified by Nile Red staining. Results During differentiation of 3T3-L1 pre-adipocytes, LPL mRNA expression increases 6-fold resulting in a 2-fold increase in cell surface-associated LPL enzymatic activity. Parallel to this increase in LPL expression, we found that intracellular lipids increased ~10-fold demonstrating a direct correlation between adipocyte-derived LPL expression and lipid storage. We next reduced LPL expression in adipocytes using siRNA transfections to directly quantify the contributions of adipocyte-derived LPL to lipid storage, This treatment reduced LPL mRNA expression and cell surface-associated LPL enzymatic activity to ~50% of non-treated controls while intracellular lipid levels were reduced by 80%. Exogenous addition of purified LPL (to restore extracellular lipolytic activity or palmitate (as a source of free fatty acids to siRNA-treated cells restored intracellular lipid levels to those measured for non

  11. Phanerochaete mutants with enhanced ligninolytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1993-06-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organopollutants in soils and aqueous media. Although some of the organic compounds are degraded under nonligninolytic conditions, most are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, biopulping, biobleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated or are hyperproducers or supersecretors of key enzymes under enriched conditions. Through ultraviolet-light and gamma-rays mutagenesis we have isolated a variety of mutants, some of which produce key enzymes of the ligninolytic system under high-nitrogen growth conditions. One of the mutants produced 272 units (U) of lignin peroxidases enzyme activity per liter after nine days under high nitrogen. The mutant and the parent strains produced up to 54 U/L and 62 U/L, respectively, of the enzyme activity under low-nitrogen growth conditions during this period. In some experiments the mutant showed 281 U/L of enzyme activity under high nitrogen after 17 days.

  12. Characterization of Lipoprotein Lipases interactions with Sortilin and SorLA

    DEFF Research Database (Denmark)

    Klinger, Stine Christensen

    fatty acids, which in turn are used as an energy source in muscle cells or as an energy reserve in adipose tissue. Lack of lipoprotein lipase leads to an elevated level of plasma lipids and results in increased risk of cardiovascular diseases. The regulation of lipoprotein lipase expression takes place...... at both transcriptional and posttranslational levels. While the transcriptional regulation of the lipase is well described, the posttranslational mechanisms affecting lipoprotein lipase expression are far from understood. The functions of the recently discovered apolipoprotein A-V are still a subject...... of discussion. Apolipoprotein A-V is a component of circulating lipoprotein particles. It is only synthesized in the liver, and plasma levels are very low compared to other apolipoproteins. Apolipoprotein A-V expression is inversely correlated to plasma triglyceride level, and a number of models have been...

  13. Cellular uptake of lipoproteins and Persistent Organic Compounds - An update and new data

    DEFF Research Database (Denmark)

    Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjærgaard; Bonefeld-Jørgensen, Eva Cecilie

    2008-01-01

    including the pesticide DDT (p,p'-dichlorodiphenyltrichloroethane), and especially its metabolite DDE (p,p'-dichlorodiphenyldichloroethene), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present...... study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors LRP (low-density lipoprotein...... receptor-related protein) and LDLR (low density lipoprotein receptor) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of LDL and [14C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks...

  14. Quantitative Lipoproteomics in Clostridium difficile Reveals a Role for Lipoproteins in Sporulation.

    Science.gov (United States)

    Charlton, Thomas M; Kovacs-Simon, Andrea; Michell, Stephen L; Fairweather, Neil F; Tate, Edward W

    2015-11-19

    Bacterial lipoproteins are surface exposed, anchored to the membrane by S-diacylglyceryl modification of the N-terminal cysteine thiol. They play important roles in many essential cellular processes and in bacterial pathogenesis. For example, Clostridium difficile is a Gram-positive anaerobe that causes severe gastrointestinal disease; however, its lipoproteome remains poorly characterized. Here we describe the application of metabolic tagging with alkyne-tagged lipid analogs, in combination with quantitative proteomics, to profile protein lipidation across diverse C. difficile strains and on inactivation of specific components of the lipoprotein biogenesis pathway. These studies provide the first comprehensive map of the C. difficile lipoproteome, demonstrate the existence of two active lipoprotein signal peptidases, and provide insights into lipoprotein function, implicating the lipoproteome in transmission of this pathogen.

  15. Behavioral versus genetic determination of lipoproteins andidentical twins discordant for exercise

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Paul T.; Blanche, Patricia J.; Krauss, Ronald M.

    2004-06-01

    Lipoprotein and weight differences between vigorously active and sedentary MZ twins are used to: (1) estimate the effects of training while controlling for genotype; (2) estimate genetic concordance in the presence of divergent lifestyles.

  16. Quantitative profiling of endocannabinoids in lipoproteins by LC-MS/MS.

    Science.gov (United States)

    Bilgin, Mesut; Bindila, Laura; Graessler, Juergen; Shevchenko, Andrej

    2015-07-01

    Endocannabinoids belong to a diverse family of endogenous lipid bioregulators acting as physiological ligands of cannabinoid receptor type 1 and cannabinoid receptor type 2 in the central and peripheral nervous system. They are also present in nmol L(-1) concentrations in human blood plasma; however, their association with possible molecular carriers remains poorly characterized. Here we report on the quantification of 46 endogenous molecular species from five major classes of endocannabinoids and endocannabinoid-related compounds in three lipoprotein fractions of human blood plasma: VLDL, LDL, HDL, and in the plasma lipoprotein-free fraction. Although sizable quantities of endocannabinoid-related molecules are associated with lipoproteins, we identified the lipoprotein-free fraction as a major carrier of endocannabinoids in blood circulation with the exception of 2-acylglycerols, which are markedly abundant in VLDL.

  17. Assessing the functional properties of high-density lipoproteins : an emerging concept in cardiovascular research

    NARCIS (Netherlands)

    Triolo, Michela; Annema, Wijtske; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    2013-01-01

    Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL cholest

  18. Polyacrylate adsorbents for the selective adsorption of cholesterol-rich lipoproteins from plasma or blood

    Directory of Open Access Journals (Sweden)

    Heuck, Claus-Chr.

    2011-01-01

    Full Text Available Polyacrylate (PAA adsorbents selectively bind low density lipoproteins (LDL from human plasma and blood, whereas very low density lipoproteins (VLDL are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw of the polyanion ligand. Ca++ and Mg++ inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL are repelled from the adsorbents due to their higher negative surface charge density.

  19. Polyacrylate adsorbents for the selective adsorption of cholesterol-rich lipoproteins from plasma or blood.

    Science.gov (United States)

    Heuck, Claus-Chr

    2011-01-24

    Polyacrylate (PAA) adsorbents selectively bind low density lipoproteins (LDL) from human plasma and blood, whereas very low density lipoproteins (VLDL) are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw) of the polyanion ligand. Ca(++) and Mg(++) inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL) are repelled from the adsorbents due to their higher negative surface charge density.

  20. Lipoprotein(a) and ischemic heart disease-A causal association? A review

    DEFF Research Database (Denmark)

    Kamstrup, P.R.

    2010-01-01

    The aim of this review is to summarize present evidence of a causal association of lipoprotein(a) with risk of ischemic heart disease (IHD). Evidence for causality includes reproducible associations of a proposed risk factor with risk of disease in epidemiological studies, evidence from in vitro...... and animal studies in support of pathophysiological effects of the risk factor, and preferably evidence from randomized clinical trials documenting reduced morbidity in response to interventions targeting the risk factor. Elevated and in particular extreme lipoprotein(a) levels have in prospective studies...... clinical trials, genetic studies, such as Mendelian randomization studies, can also support claims of causality. Levels of lipoprotein(a) are primarily determined by variation in the LPA gene coding for the apolipoprotein(a) moiety of lipoprotein(a), and genetic epidemiologic studies have documented...

  1. Simvastatin but not bezafibrate decreases plasma lipoprotein-associated phospholipase A(2) mass in type 2 diabetes mellitus : Relevance of high sensitive C-reactive protein, lipoprotein profile and low-density lipoprotein (LDL) electronegativity

    NARCIS (Netherlands)

    Constantinides, Alexander; de Vries, Rindert; van Leeuwen, Jeroen J. J.; Gautier, Thomas; van Pelt, L. Joost; Tselepis, Alexandros D.; Lagrost, Laurent; Dullaart, Robin P. F.

    2012-01-01

    Objective: Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels predict incident cardiovascular disease, impacting Lp-PLA(2) as an emerging therapeutic target. We determined Lp-PLA(2) responses to statin and fibrate administration in type 2 diabetes mellitus, and assessed relationship

  2. Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.

    NARCIS (Netherlands)

    Tits, L.J.H. van; Smilde, T.J.; Wissen, S. van; Graaf, J. de; Kastelein, J.J.P.; Stalenhoef, A.F.H.

    2004-01-01

    BACKGROUND: Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. METHODS: In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose

  3. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    OpenAIRE

    Shou-Kui Xiang; Fei Hua; Ying Tang; Xiao-Hong Jiang; Qi Zhuang; Feng-Juan Qian

    2012-01-01

    Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS). Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total testosterone (T), fasting glucose (FBG), fasting insulin (FINS), serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lip...

  4. Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Eckoldt, J.; Winkler, K.;

    2014-01-01

    So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration...... with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions....

  5. Preparation and Adsorption Properties of PAM Based Adsorbents for Plasma Lipoproteins

    Institute of Scientific and Technical Information of China (English)

    Hai Tao LI; Zhi YUAN; Xin Fu CHEN; Bin LIU; Bin SHEN; Bing Lin HE

    2004-01-01

    Crosslinked macroporous polyacrylamide(PAM)was prepared with inverse phase suspension polymerization technique.After treatment with hydrazine,the polymer was functionalized with chloroacetic acid,trifluoroacetic acid diethylenetriaminepentaacetic acid (DEPAA), and maleic acid, respectively,and PAM based adsorbents bearing carboxyl functional groups for low density lipoprotein(LDL)apheresis use were obtained.The blood compatibility and the adsorption properties for plasma lipoproteins of PAM based adsorbents were investigated.

  6. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance

    OpenAIRE

    Kim, Jason K.; Fillmore, Jonathan J.; Chen, Yan; Yu, Chunli; Moore, Irene K.; Pypaert, Marc; Lutz, E. Peer; Kako, Yuko; Velez-Carrasco, Wanda; Goldberg, Ira J.; Breslow, Jan L.; Shulman, Gerald I.

    2001-01-01

    Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic–euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. Muscle–lipoprotein lipase mice had a 3...

  7. Simulated lipoprotein transport in the wall of branched arteries.

    Science.gov (United States)

    Darbeau, M Z; Lutz, R J; Collins, W E

    2000-01-01

    Study of arterial blood flow dynamics improves our understanding of the development of cardiovascular diseases such as atherosclerosis. The transport and accumulation of macromolecules in the arterial wall can be influenced by local fluid mechanics. We used numeric simulations to investigate such transport in a T-junction model. Presumably an in vitro experiment would consist of gel segments inserted in the walls of a mechanical flow T-junction model near branch points where separation and recirculation zones are expected. The transport of low density lipoprotein (LDL) was investigated theoretically at these sites in a two dimensional numeric T-branch model. In the numeric model, the hydraulic conductivity of the porous gel wall segments was varied for a fixed species diffusivity to provide simulations with wall transmural Peclet numbers ranging from 0.3 to 30. Steady state flow patterns in the lumen of the two dimensional T-branch were simulated at Reynolds numbers of 250 and 500, using the software package FIDAP 7.61 to implement the finite element method. The simulations demonstrated that wall Peclet numbers greater than 1.0 were needed to achieve species concentration gradients within the wall that varied in the axial direction, thereby reflecting the influence of disturbed flow and pressure patterns in the lumen. As expected, the transmural concentration gradients were steeper when convection predominated. Blood flow in the lumen can influence the distribution of macromolecules in the arterial wall and needs to be investigated for the relevance to atherosclerosis.

  8. Serum lipoproteins of patients with glycogen storage disease.

    Science.gov (United States)

    Rosenfeld, E L; Chibisov, I V; Karmansky, I M; Tabolin, V A; Chistova, L V; Leontiev, A F

    1980-03-14

    Seventeen patients with different types of glycogen storage disease (GSD) were under observation. The type of the disease was defined from glucaemic and lactotaemic curves obtained in glucose, galactose and adrenaline tolerance tests and by biochemical analysis of liver biopsy specimens. Seven patients were found to have Type I; five patients, Type III; one patient, Type VI; and four patients, the Type IX (or X) of GSD. The serum lipoprotein (LP) content was determined in all patients using analytical ultracentrifugation. Hyperlipoproteinaemia (HLP) was found in virtually all patients. Patients with Type I of GSD were found to have Types 2b and 4 of HLP; and patients with Type III of GSD, 2b Type of HLP. 2a Type of HLP was diagnosed in patients with GSD of VI and IX (X) Types. Patients with Type III GSD, in contrast to those with GSD of other types, had enhanced levels of Sf 12-20 LP. The levels of Sf 100-400 and Sf 20-100 LP were greatly increased only in patients with Type I GSD.

  9. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

    Science.gov (United States)

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

    2010-01-01

    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  10. Low fasting low high-density lipoprotein and postprandial lipemia

    Directory of Open Access Journals (Sweden)

    Sorodila Konstandina

    2004-07-01

    Full Text Available Abstract Background Low levels of high density lipoprotein (HDL cholesterol and disturbed postprandial lipemia are associated with coronary heart disease. In the present study, we evaluated the variation of triglyceride (TG postprandially in respect to serum HDL cholesterol levels. Results Fifty two Greek men were divided into 2 main groups: a the low HDL group (HDL p = 0.002. The low HDL group had significantly higher TG at 4, 6 and 8 h postprandially compared to the controls (p = 0.006, p = 0.002, and p p = 0.017 compared to the matched-control group. ROC analysis showed that fasting TG ≥ 121 mg/dl have 100% sensitivity and 81% specificity for an abnormal TG response (auc = 0.962, p Conclusions The delayed TG clearance postprandially seems to result in low HDL cholesterol even in subjects with low fasting TG. The fasting TG > 121 mg/dl are predictable for abnormal response to fatty meal.

  11. Lipoprotein(a) and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Mora, Samia; Kamstrup, Pia R; Rifai, Nader;

    2010-01-01

    (a) concentrations and incident type 2 diabetes (n = 1670) for a follow-up period of 13 years. We confirmed our findings in 9652 Danish men and women with prevalent diabetes (n = 419). Analyses were adjusted for risk factors that included age, race, smoking, hormone use, family history, blood pressure, body mass......BACKGROUND: Previous studies have demonstrated that cardiovascular risk is higher with increased lipoprotein (a) [Lp(a)]. Whether Lp(a) concentration is related to type 2 diabetes is unclear. METHODS: In 26 746 healthy US women (mean age 54.6 years), we prospectively examined baseline Lp...... index, hemoglobin A(1c) (Hb A(1c)), C-reactive protein, and lipids. RESULTS: Lp(a) was inversely associated with incident diabetes, with fully adjusted hazard ratios (HRs) and 95% CIs for quintiles 2-5 vs quintile 1 of 0.87 (0.75-1.01), 0.80 (0.68-0.93), 0.88 (0.76-1.02), and 0.78 (0.67-0.91); P...

  12. Lipoprotein(a) and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Mora, S.; Kamstrup, Pia R; Rifai, N.;

    2010-01-01

    BACKGROUND: Previous studies have demonstrated that cardiovascular risk is higher with increased lipoprotein (a) [Lp(a)]. Whether Lp(a) concentration is related to type 2 diabetes is unclear. METHODS: In 26 746 healthy US women (mean age 54.6 years), we prospectively examined baseline Lp......(a) concentrations and incident type 2 diabetes (n = 1670) for a follow-up period of 13 years. We confirmed our findings in 9652 Danish men and women with prevalent diabetes (n = 419). Analyses were adjusted for risk factors that included age, race, smoking, hormone use, family history, blood pressure, body mass...... index, hemoglobin A(1c) (Hb A(1c)), C-reactive protein, and lipids. RESULTS: Lp(a) was inversely associated with incident diabetes, with fully adjusted hazard ratios (HRs) and 95% CIs for quintiles 2-5 vs quintile 1 of 0.87 (0.75-1.01), 0.80 (0.68-0.93), 0.88 (0.76-1.02), and 0.78 (0.67-0.91); P...

  13. [Effects of antihypertensive agents on lipoproteins and thrombocyte function].

    Science.gov (United States)

    Birkebaek, N H

    1990-09-24

    This article is a review of the literature concerning the effects of antihypertensive agents on the lipid status and thrombocyte function. Many investigations have revealed that thiazide diuretics, non-selective beta-blockers and beta-1 selective beta-blockers have resulted in alteration of lipids in a potentially atherogenic direction. Only thiazide diruetics have caused increase in low density lipoprotein, which is causally connected with increased tendency to atheroschlerosis. In some investigations, alpha-1 blockers have had a favourable effect on lipids in an atherogenic direction. Other antihypertensive agents appear, by and large, to be lipid neutral even although isolated investigations have demonstrated displacement of lipids both in positive and negative directions. Non-selective beta-blockers appear to alter thrombocyte function towards a greater tendency to aggregation while beta-1 selective beta-blockers are neutral. Ca-antagonists, angiotensin converting enzyme inhibitors and ketanserin have, theoretically, anti-aggregatory effects on the thrombocytes but only few ex vivo and in vivo experiments have confirmed this effect. Monitoring of lipids is recommended before and after antihypertensive treatment. Finally, the effect on thrombocyte function should be considered in the choice of hypertensive agent.

  14. Probucol alleviates atherosclerosis and improves high density lipoprotein function

    Directory of Open Access Journals (Sweden)

    Zhong Jian-Kai

    2011-11-01

    Full Text Available Abstract Background Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C. However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function. Methods Eighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [3H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks. Results Compared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased. Conclusion Probucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions.

  15. High-density lipoprotein endocytosis in endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Stefanie; Fruhwürth; Margit; Pavelka; Robert; Bittman; Werner; J; Kovacs; Katharina; M; Walter; Clemens; Rhrl; Herbert; Stangl

    2013-01-01

    AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

  16. Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.

    Science.gov (United States)

    Schinella, Guillermo R; Tournier, Horacio A; Máñez, Salvador; de Buschiazzo, Perla M; Del Carmen Recio, María; Ríos, José Luis

    2007-01-01

    Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). In conclusion, tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol.

  17. Iatrogenic severe depression of high-density lipoprotein cholesterol.

    Science.gov (United States)

    Mymin, D; Dembinski, T; Friesen, M H

    2009-07-01

    The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol.

  18. Escherichia coli lipoprotein binds human plasminogen via an intramolecular domain

    Directory of Open Access Journals (Sweden)

    Tammy eGonzalez

    2015-10-01

    Full Text Available Escherichia coli lipoprotein (Lpp is a major cellular component that exists in two distinct states, bound-form and free-form. Bound-form Lpp is known to interact with the periplasmic bacterial cell wall, while free-form Lpp is localized to the bacterial cell surface. A function for surface-exposed Lpp has yet to be determined. We hypothesized that the presence of C-terminal lysines in the surface-exposed region of Lpp would facilitate binding to the host zymogen plasminogen, a protease commandeered by a number of clinically important bacteria. Recombinant Lpp was synthesized and the binding of Lpp to plasminogen, the effect of various inhibitors on this binding, and the effects of various mutations of Lpp on Lpp-plasminogen interactions were examined. Additionally, the ability of Lpp-bound plasminogen to be converted to active plasmin was analyzed. We determined that Lpp binds plasminogen via an atypical domain located near the center of mature Lpp that may not be exposed on the surface of intact E. coli according to the current localization model. Finally, we found that plasminogen bound by Lpp can be converted to active plasmin. While the consequences of Lpp binding plasminogen are unclear, these results prompt further investigation of the ability of surface exposed Lpp to interact with host molecules such as extracellular matrix components and complement regulators, and the role of these interactions in infections caused by E. coli and other bacteria.

  19. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    Science.gov (United States)

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions.

  20. Native low density lipoprotein promotes lipid raft formation in macrophages.

    Science.gov (United States)

    Song, Jian; Ping, Ling-Yan; Duong, Duc M; Gao, Xiao-Yan; He, Chun-Yan; Wei, Lei; Wu, Jun-Zhu

    2016-03-01

    Oxidized low‑density lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cell‑mediated LDL oxidation remain to be elucidated. The present study investigated whether native‑LDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methyl‑β‑cyclodextrin (MβCD), LDL‑stimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MβCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to label‑free quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following native‑LDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that native‑LDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation.

  1. Fully mechanized latex immunoassay for serum lipoprotein(a).

    Science.gov (United States)

    Abe, A; Yoshimura, Y; Sekine, T; Maeda, S; Yamashita, S; Noma, A

    1994-03-01

    We have developed a fully automated system to quantify lipoprotein(a) (Lp(a)) in human serum, based on the latex-enhanced turbidimetric immunoassay by application of the Immuno Chemistry Analyzer 501X. This assay was carried out with undiluted serum and was able to detect at Lp(a) levels higher than 4.0 mg/l. When judged to be out of range of the calibration (> 600 mg/l), the sample was automatically re-tested after automatic 10-fold dilution. Within-run C.V.s ranged from 1.9 to 2.1% and between-run C.V.s from 2.7 to 3.9%. Results by the present method were in good agreement with those by the in-house ELISA (r = 0.978) and the commercial ELISA (r = 0.990). The distribution of Lp(a) levels in sera from 508 healthy donors was highly skewed; the mean and median were 158 mg/l and 105 mg/l, respectively.

  2. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    Science.gov (United States)

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  3. Lipoprotein(a: Cellular Effects and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Kirsten Riches

    2012-01-01

    Full Text Available Lipoprotein(a (Lp(a is an independent risk factor for the development of cardiovascular disease (CVD. Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a apart from plasma apheresis, which is costly and labour intensive. The Lp(a molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a (apo(a, both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC and endothelial cells (EC. Therefore, it is of key importance to determine the molecular pathways by which Lp(a exerts its influence on the vascular system in order to design therapeutics to target its cellular effects. This paper will summarise the role of Lp(a in modulating cell behaviour in all aspects of the vascular system including platelets, monocytes, SMC, and EC.

  4. Adropin induction of lipoprotein lipase expression in tilapia hepatocytes.

    Science.gov (United States)

    Lian, Anji; Wu, Keqiang; Liu, Tianqiang; Jiang, Nan; Jiang, Quan

    2016-01-01

    The peptide hormone adropin plays a role in energy homeostasis. However, biological actions of adropin in non-mammalian species are still lacking. Using tilapia as a model, we examined the role of adropin in lipoprotein lipase (LPL) regulation in hepatocytes. To this end, the structural identity of tilapia adropin was established by 5'/3'-rapid amplification of cDNA ends (RACE). The transcripts of tilapia adropin were ubiquitously expressed in various tissues with the highest levels in the liver and hypothalamus. The prolonged fasting could elevate tilapia hepatic adropin gene expression, whereas no effect of fasting was observed on hypothalamic adropin gene levels. In primary cultures of tilapia hepatocytes, synthetic adropin was effective in stimulating LPL release, cellular LPL content, and total LPL production. The increase in LPL production also occurred with parallel rises in LPL gene levels. In parallel experiments, adropin could elevate cAMP production and up-regulate protein kinase A (PKA) and PKC activities. Using a pharmacological approach, cAMP/PKA and PLC/inositol trisphosphate (IP3)/PKC cascades were shown to be involved in adropin-stimulated LPL gene expression. Parallel inhibition of p38MAPK and Erk1/2, however, were not effective in these regards. Our findings provide, for the first time, evidence that adropin could stimulate LPL gene expression via direct actions in tilapia hepatocytes through the activation of multiple signaling mechanisms.

  5. A novel lipoprotein nanoparticle system for membrane proteins

    Science.gov (United States)

    Frauenfeld, Jens; Löving, Robin; Armache, Jean-Paul; Sonnen, Andreas; Guettou, Fatma; Moberg, Per; Zhu, Lin; Jegerschöld, Caroline; Flayhan, Ali; Briggs, John A.G.; Garoff, Henrik; Löw, Christian; Cheng, Yifan; Nordlund, Pär

    2016-01-01

    Membrane proteins are of outstanding importance in biology, drug discovery and vaccination. A common limiting factor in research and applications involving membrane proteins is the ability to solubilize and stabilize membrane proteins. Although detergents represent the major means for solubilizing membrane proteins, they are often associated with protein instability and poor applicability in structural and biophysical studies. Here, we present a novel lipoprotein nanoparticle system that allows for the reconstitution of membrane proteins into a lipid environment that is stabilized by a scaffold of Saposin proteins. We showcase the applicability of the method on two purified membrane protein complexes as well as the direct solubilization and nanoparticle-incorporation of a viral membrane protein complex from the virus membrane. We also demonstrate that this lipid nanoparticle methodology facilitates high-resolution structural studies of membrane proteins in a lipid environment by single-particle electron cryo-microscopy (cryo-EM) and allows for the stabilization of the HIV-envelope glycoprotein in a functional state. PMID:26950744

  6. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja X; McCormick, Sally P; Tsimikas, Sotirios

    2010-01-01

    lipoprotein-associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n...... = 19), human apoB-100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo...... with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia....

  7. Inhibitory effect of morinda citrifolia L. On lipoprotein lipase activity.

    Science.gov (United States)

    Pak-Dek, M S; Abdul-Hamid, A; Osman, A; Soh, C S

    2008-10-01

    Efficacy of Morinda citrifolia L. leaf (MLE) and fruit extracts (MFE) in inhibiting lipoprotein lipase (LPL) was determined in vitro. The result of the study showed that the highest inhibition on the LPL activity was exhibited by MLE (66%+/- 2.1%), which is significantly higher than that demonstrated by MFE (54.5%+/- 2.5%), green tea extract (GTE) (54.5%+/- 2.6%), and catechin (43.6%+/- 6.1%). Percent of LPL inhibition increase with concentration of the extracts. Quantitative analysis of the extracts revealed the presence of high levels of (+)-catechin at 63.5 +/- 17 and 53.7 +/- 5.7 mg/g in MLE and MFE, respectively, although not as high as that found in GTE (530.6 +/- 42 mg/g). Appreciable amount of epicatechin was found in all extracts tested, while rutin was only found in MLE and MFE. The study suggested that both leaf and fruit of M. citrifolia may be used as antiobesity agents in body weight management.

  8. Enhanced cellulase production in mutants of Thermomonospora

    Energy Technology Data Exchange (ETDEWEB)

    Fennington, G.; Lupo, D.; Stutzenberger, F.

    1982-01-01

    Thermomonospora curvata, a thermophilic actinomycete, secretes multiple forms of endo-beta, 1-4-glucanase (EG) when grown on cellulose-mineral salts liquid medium. The EG activity (measured as carboxymethyl cellulose hydrolysis) was separated by ion exchange chromatography into three distinct components which differed in their kinetic properties. Exposure of T. curvata to ultraviolet light, N-nitrosoguanidine, or ethane methyl sulfonate produced mutants with enhanced EG production. Selection of colonies which cleared cellulose agar plants containing 2-deoxyglucose or glycerol yielded mutants having 1.5 to 2.6 times the extracellular EG and saccharifying activity (measured by filter-paper and cotton-fiber hydrolysis). The secretion of extracellular protein was increased proportionally in mutant cultures. (Refs. 40).

  9. Lipoprotein Abnormalities in Cholestasis I. Electro-phoretic and Ultracentrifugal Analyses

    Directory of Open Access Journals (Sweden)

    Watanabe,Makoto

    1979-08-01

    Full Text Available The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y, LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.

  10. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL

    Science.gov (United States)

    Jorissen, Winde; Wouters, Elien; Bogie, Jeroen F.; Vanmierlo, Tim; Noben, Jean-Paul; Sviridov, Denis; Hellings, Niels; Somers, Veerle; Valcke, Roland; Vanwijmeersch, Bart; Stinissen, Piet; Mulder, Monique T.; Remaley, Alan T.; Hendriks, Jerome J. A.

    2017-01-01

    Lipoproteins modulate innate and adaptive immune responses. In the chronic inflammatory disease multiple sclerosis (MS), reports on lipoprotein level alterations are inconsistent and it is unclear whether lipoprotein function is affected. Using nuclear magnetic resonance (NMR) spectroscopy, we analysed the lipoprotein profile of relapsing-remitting (RR) MS patients, progressive MS patients and healthy controls (HC). We observed smaller LDL in RRMS patients compared to healthy controls and to progressive MS patients. Furthermore, low-BMI (BMI ≤ 23 kg/m2) RRMS patients show increased levels of small HDL (sHDL), accompanied by larger, triglyceride (TG)-rich VLDL, and a higher lipoprotein insulin resistance (LP-IR) index. These alterations coincide with a reduced serum capacity to accept cholesterol via ATP-binding cassette (ABC) transporter G1, an impaired ability of HDL3 to suppress inflammatory activity of human monocytes, and modifications of HDL3’s main protein component ApoA-I. In summary, lipoprotein levels and function are altered in RRMS patients, especially in low-BMI patients, which may contribute to disease progression in these patients. PMID:28230201

  11. [Serum lipid and lipoprotein fractions in 2 age groups of male rabbits].

    Science.gov (United States)

    Kiriakov, A; Tinterova, Z; Stoianova, S; Kavrŭkova, Iu; Rashev, M

    1980-01-01

    The authors examined in 125 young sexually mature and in 50 young sexually immature male rabbits of a New Zealand improved Bulgarian breed the following serum lipid indices: total lipids, total and free cholesterol triglycerides, phospholipids, cholesterol and triglyceride content of VLDL (very low density lipoproteins), LDL (high density lipoproteins), HDL (high density lipoproteins) and the percentage concentration of serum lipopropteins, examined electrophoretically. The concentrations of the examined lipid and lipoprotein fractions in the sera of both age groups of rabbits showed asymetrical distribution. The hystograms of the total lipids and total cholesterol in younger animals was excluded. The logarithnictrandsformation of asymetricaly distributed concentrations of the examined fractions normalized their distribution in a part of them. The authors determined the ranges of the norm with the help of the percentile analysis in the remaining indices with asymetric distribution. Serum lipid and lipoprotein profile revealed substantial differnces in both age groups of animals. Serum lipids and lipoproteins in young sexually mature male rabbits differed from those of a man not only by their absolute concentrations, but also by their structural characteristics.

  12. Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

    Science.gov (United States)

    Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

    2006-01-01

    Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

  13. Lycopene stabilizes lipoprotein levels during D-galactosamine/lipopolysaccharide induced hepatitis in experimental rats

    Institute of Scientific and Technical Information of China (English)

    Sheik Abdulazeez Sheriff; Thiruvengadam Devaki

    2012-01-01

    Objective: To investigate the effect of lycopene on lipoprotein metabolism during D-galactosamine/lipopolysaccharide (D-Gal/LPS) induced hepatitis in experimental rats. Methods: The efficacy of lycopene was validated during D-Gal/LPS induced hepatitis by analyzing the activity of lipid metabolizing enzymes such as lipoprotein lipase (LPL), lecithin-cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). Lipo protein analyses were done by the estimation of very low density lipoprotein cholesterol (VLDL), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Results: The toxic insult of D-galactosamine/lipopolysaccharide (D-Gal/LPS) in experimental group of animals reduces the normal values of lipid metabolizing enzymes due to liver injury. The significant drop in the levels of HDL and concomitant increase in the values of VLDL and LDL were observed. The pretreatment of lycopene restore these altered values to near normal level in experimental group of animals. Conclusions: In the light of results, it can be concluded that administration lycopene stabilizes the lipoprotein levels by regulating the lipid metabolizing enzymes through its antioxidant defense and helps to maintain the normal lipid metabolism during toxic injury in liver.

  14. Aging Kit mutant mice develop cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Lei Ye

    Full Text Available Both bone marrow (BM and myocardium contain progenitor cells expressing the c-Kit tyrosine kinase. The aims of this study were to determine the effects of c-Kit mutations on: i. myocardial c-Kit(+ cells counts and ii. the stability of left ventricular (LV contractile function and structure during aging. LV structure and contractile function were evaluated (echocardiography in two groups of Kit mutant (W/Wv and W41/W42 and in wild type (WT mice at 4 and 12 months of age and the effects of the mutations on LV mass, vascular density and the numbers of proliferating cells were also determined. In 4 month old Kit mutant and WT mice, LV ejection fractions (EF and LV fractional shortening rates (FS were comparable. At 12 months of age EF and FS were significantly decreased and LV mass was significantly increased only in W41/W42 mice. Myocardial vascular densities and c-Kit(+ cell numbers were significantly reduced in both mutant groups when compared to WT hearts. Replacement of mutant BM with WT BM at 4 months of age did not prevent these abnormalities in either mutant group although they were somewhat attenuated in the W/Wv group. Notably BM transplantation did not prevent the development of cardiomyopathy in 12 month W41/W42 mice. The data suggest that decreased numbers and functional capacities of c-Kit(+ cardiac resident progenitor cells may be the basis of the cardiomyopathy in W41/W42 mice and although defects in mutant BM progenitor cells may prove to be contributory, they are not causal.

  15. Behavioral characterization of system xc- mutant mice.

    Science.gov (United States)

    McCullagh, Elizabeth A; Featherstone, David E

    2014-05-15

    The slc7a11 gene encodes xCT, an essential component of 'system xc-', a plasma membrane exchanger that imports cystine and exports glutamate. Slc7a11 is expressed primarily in the brain, but its role there is not clear. We performed behavioral tests on two different strains of homozygous slc7a11 mutant mice ('sut' and 'xCT'), as well as heteroallelic offspring of these two strains ('xCT/sut') and their associated genetic backgrounds. Homozygous sut mutant males showed reduced spontaneous alternation in spontaneous alternation tasks as well as reduced movement in an open field maze, but xCT and xCT/sut strains did not show significant changes in these tasks compared to appropriate controls. Neither xCT nor sut mutants showed differences from controls in rotarod tests. Female behavioral phenotypes were independent of estrus cycle stage. To ensure that homozygous xCT, sut, and xCT/sut strains all represent protein null alleles, we measured whole brain xCT protein levels using immunoblots. xCT, sut and xCT/sut strains showed no detectable xCT protein expression, confirming them as null alleles. Previously published microdialysis experiments showed reduced striatal glutamate in xCT mutants. Using the same methods, we measured reduced interstitial glutamate levels in the striatum but not cerebellum of sut mutants. However, we detected no glutamate change in the striatum or cerebellum of sut/xCT mice. We detected no changes in whole brain EAAT-1, -2, or -3 expression. We conclude that the behavioral and chemical differences exist between slc7a11 mutant strains, but we were unable to definitively attribute any of these differences to loss of system xc-.

  16. A New Species of Weltrichia Braun in North China with a Special Bennettitalean Male Reproductive Organ%本内苏铁类雄性生殖器官Weltrichia属一新种

    Institute of Scientific and Technical Information of China (English)

    李楠; 李勇; 王丽霞; 郑少林; 张武

    2004-01-01

    报道了本内苏铁类雄性生殖器官Weltrichia属的一个新种--Weltrichia daohugouensis sp.nov.,标本发现于内蒙古宁城山头乡道虎沟村附近的中侏罗统海房沟组.它是一个分离保存的本内苏铁类单性雄球花(球穗花序),在侧向压缩的平面上展开,呈扇形.基部球花梗未保存,下部由11个窄楔形的裂片融合成漏斗状或杯状,上部裂开成数目相等的游离的小孢子叶.每个小孢子叶的上部有两列花粉囊.文中对新种进行了详细地描述和讨论.并对W.huangbanjigouensis Su et Zheng的鉴定特征进行了修订.%We report a new species of the genus Weltrichia Braun with a special Bennettitalean male reproductive organ-W. daohugouensis Li et Zheng sp. nov., which was discovered from Haifanggou Formation (Middle Jurassic) in Daohugou Village, Shantou Town, Ningcheng County, Inner Mongolia (Nei Mongol)Autonomous Region, China. It is a unisexual male strobile which was a laterally compressed preserved specimen being fan-shaped and appearing as half of a whole. Its base and peduncle are lost while the lower part of the strobile consists of eleven narrowly wedged segments fused together into a funnel or cup-like.In the upper part of the strobile these segments separate into free structure (microsporophylls), each bearing two rows of pollen sacs (synangia). In this paper a new species W. daohugouensis Li et Zheng sp.nov. is described and the identification of the W. huangbanjigouensis Sun et Zheng is emended.

  17. Green tea catechins prevent low-density lipoprotein oxidation via their accumulation in low-density lipoprotein particles in humans.

    Science.gov (United States)

    Suzuki-Sugihara, Norie; Kishimoto, Yoshimi; Saita, Emi; Taguchi, Chie; Kobayashi, Makoto; Ichitani, Masaki; Ukawa, Yuuichi; Sagesaka, Yuko M; Suzuki, Emiko; Kondo, Kazuo

    2016-01-01

    Green tea is rich in polyphenols, including catechins which have antioxidant activities and are considered to have beneficial effects on cardiovascular health. In the present study, we investigated the effects of green tea catechins on low-density lipoprotein (LDL) oxidation in vitro and in human studies to test the hypothesis that catechins are incorporated into LDL particles and exert antioxidant properties. In a randomized, placebo-controlled, double-blind, crossover trial, 19 healthy men ingested green tea extract (GTE) in the form of capsules at a dose of 1 g total catechin, of which most (>99%) was the gallated type. At 1 hour after ingestion, marked increases of the plasma concentrations of (-)-epigallocatechin gallate and (-)-epicatechin gallate were observed. Accordingly, the plasma total antioxidant capacity was increased, and the LDL oxidizability was significantly reduced by the ingestion of GTE. We found that gallated catechins were incorporated into LDL particles in nonconjugated forms after the incubation of GTE with plasma in vitro. Moreover, the catechin-incorporated LDL was highly resistant to radical-induced oxidation in vitro. An additional human study with 5 healthy women confirmed that GTE intake sufficiently increased the concentration of gallated catechins, mainly in nonconjugated forms in LDL particles, and reduced the oxidizability of LDL. In conclusion, green tea catechins are rapidly incorporated into LDL particles and play a role in reducing LDL oxidation in humans, which suggests that taking green tea catechins is effective in reducing atherosclerosis risk associated with oxidative stress.

  18. Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

    Science.gov (United States)

    Thomas, M J; Chen, Q; Zabalawi, M; Anderson, R; Wilson, M; Weinberg, R; Sorci-Thomas, M G; Rudel, L L

    2001-02-13

    This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.

  19. A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

    • BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
    • METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
    • RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
    • CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

    • Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism.

      Science.gov (United States)

      Dashty, M; Motazacker, M M; Levels, J; de Vries, M; Mahmoudi, M; Peppelenbosch, M P; Rezaee, F

      2014-03-03

      Apart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL- and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti- microbial proteins. Prothrombin, protein S, fibrinogen γ, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen α chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 - dyslipidaemia, 2 - atherosclerosis and vascular disease, and 3 - coagulation disorders.

  1. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  2. Different effects of diets rich in olive oil, rapeseed oil and sunflower-seed oil on postprandial lipid and lipoprotein concentrations and on lipoprotein oxidation susceptibility

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall; Pedersen, A.; Sandstrøm, B.

    2002-01-01

    oxidation of fasting and postprandial lipoproteins eighteen males consumed diets enriched with rapeseed oil (RO), olive oil (OO), or sunflower-seed oil (SO) in randomised order for periods of 3 weeks followed by a RO test meal. In the postprandial state the concentrations of cholesterol and triacylglycerol...

  3. A dominant semi dwarf mutant in rice

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ In the winter of 1997, a semi dwarf mutant was found in the F6 population of M9056/ R8018 xuan in Hainan Province. In the spring of 1998, the seeds were sown in Hefei, Anhui Province and the plant height of the population was measured at maturity.

  4. Nicotinamide ribosyl uptake mutants in Haemophilus influenzae.

    Science.gov (United States)

    Herbert, Mark; Sauer, Elizabeta; Smethurst, Graeme; Kraiss, Anita; Hilpert, Anna-Karina; Reidl, Joachim

    2003-09-01

    The gene for the nicotinamide riboside (NR) transporter (pnuC) was identified in Haemophilus influenzae. A pnuC mutant had only residual NR uptake and could survive in vitro with high concentrations of NR, but could not survive in vivo. PnuC may represent a target for the development of inhibitors for preventing H. influenzae disease.

  5. Colored HOMFLY polynomials can distinguish mutant knots

    CERN Document Server

    Nawata, Satoshi; Singh, Vivek Kumar

    2015-01-01

    We illustrate from the viewpoint of braiding operations on WZNW conformal blocks how colored HOMFLY polynomials with multiplicity structure can detect mutations. As an example, we explicitly evaluate the (2,1)-colored HOMFLY polynomials that distinguish a famous mutant pair, Kinoshita-Terasaka and Conway knot.

  6. High-density lipoprotein and atherosclerosis: Roles of lipid transporters

    Institute of Scientific and Technical Information of China (English)

    Yoshinari; Uehara; Keijiro; Saku

    2014-01-01

    Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

  7. Oxidative stress and plasma lipoproteins in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Maia, Fernanda Maria Machado; Santos, Emanuelly Barbosa; Reis, Germana Elias [Universidade Estadual do Ceará, Fortaleza, CE (Brazil)

    2014-07-01

    To evaluate the relation between oxidative stress and lipid profile in patients with different types of cancer. This was an observational cross-sectional. A total of 58 subjects were evaluated, 33 males, divided into two groups of 29 patients each: Group 1, patients with cancer of the digestive tract and accessory organs; Group 2 patients with other types of cancers, all admitted to a public hospital. The plasma levels (lipoproteins and total cholesterol, HDL, and triglycerides, for example) were analyzed by enzymatic kits, and oxidative stress based on thiobarbituric acid-reactive substances, by assessing the formation of malondialdehyde. In general the levels of malondialdehyde of patients were high (5.00μM) as compared to 3.31μM for healthy individuals. The median values of lipids exhibited normal triacylglycerol (138.78±89.88mg/dL), desirable total cholesterol values (163.04±172.38mg/dL), borderline high LDL (151.30±178.25mg/dL) and low HDL (31.70±22.74mg/dL). Median HDL levels in Group 1 were lower (31.32mg/dL) than the cancer patients in Group 2 (43.67mg/dL) (p=0.038). Group 1 also showed higher levels of oxidative stress (p=0.027). The lipid profile of patients with cancer was not favorable, which seems to have contributed to higher lipid peroxidation rate, generating a significant oxidative stress.

  8. High-density lipoprotein proteome dynamics in human endotoxemia

    Directory of Open Access Journals (Sweden)

    Stroes Erik SG

    2011-06-01

    Full Text Available Abstract Background A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L and 10 men with high HDL cholesterol levels (1.9+/-0.4 mmol/L were challenged with endotoxin (LPS intravenously (1 ng/kg bodyweight. We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome. Results Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value Conclusions This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.

  9. Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations

    Science.gov (United States)

    Cardoso-Saldaña, Guillermo; De La Peña-Díaz, Aurora; Zamora-González, José; Gomez-Ortega, Rocio; Posadas-Romero, Carlos; Izaguirre-Avila, Raul; Malvido-Miranda, Elsa; Morales-Anduaga, Maria Elena; Angles-Cano, Eduardo

    2006-01-01

    Background Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin-binding with plasminogen inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a), have been reported in several populations. Aim To study the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. Methods We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin-binding by immuno-enzymatic assay and STR polymorphic markers genetic analysis by capillary electrophoresis. Results Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg/dL) relative to Mazahuas (8.2 mg/dL), Mayas (8.25 mg/dL) and Mayos (6.5 mg/dL). Phenotype distribution was different in Mayas and Mazahuas as compared to the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. Conclusion There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in Native Mexican and the Mestizo group. PMID:16684693

  10. Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Toshihito Kosaka; Taizou Shiraishi; Masatoshi Watanabe; Takayuki Yamamoto; Ai Nakahara; Takahiko Katoh; Junji Yoshino; Kazuo Inui; Takao Wakabayashi; Kazumu Okushima; Takashi Kobayashi; Hironao Miyoshi; Yuta Nakamura; Shigekazu Hayashi

    2006-01-01

    AIM: To examine the influence of lipoprotein lipase (LPL)gene polymorphism in ulcerative colitis (UC) patients.METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing.Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR= 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more numerous than those with H+/+ genotype (OR = 2.51, 95%CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI =1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for Pvu Ⅱ polymorphism (P< 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.CONCLUSION: Ser447stop and HindⅢ LPL polymorphisms may influence age of onset of UC, while HindⅢand PvuⅡ polymorphisms influence serum triglyceride in UC patients.

  11. Polizei-Compliance / Frank Braun, Florian Albrecht

    Index Scriptorium Estoniae

    Braun, Frank

    2015-01-01

    Normide ja seaduste järgimisest politsei tegevuses ning vastavussüsteemi juurutamisest politseiorganisatsioonis tegevuse läbipaistvamaks muutmiseks, halduse optimeerimiseks ja kodanike usalduse suurendamiseks

  12. GAMPMS: Genetic algorithm managed peptide mutant screening.

    Science.gov (United States)

    Long, Thomas; McDougal, Owen M; Andersen, Tim

    2015-06-30

    The prominence of endogenous peptide ligands targeted to receptors makes peptides with the desired binding activity good molecular scaffolds for drug development. Minor modifications to a peptide's primary sequence can significantly alter its binding properties with a receptor, and screening collections of peptide mutants is a useful technique for probing the receptor-ligand binding domain. Unfortunately, the combinatorial growth of such collections can limit the number of mutations which can be explored using structure-based molecular docking techniques. Genetic algorithm managed peptide mutant screening (GAMPMS) uses a genetic algorithm to conduct a heuristic search of the peptide's mutation space for peptides with optimal binding activity, significantly reducing the computational requirements of the virtual screening. The GAMPMS procedure was implemented and used to explore the binding domain of the nicotinic acetylcholine receptor (nAChR) α3β2-isoform with a library of 64,000 α-conotoxin (α-CTx) MII peptide mutants. To assess GAMPMS's performance, it was compared with a virtual screening procedure that used AutoDock to predict the binding affinity of each of the α-CTx MII peptide mutants with the α3β2-nAChR. The GAMPMS implementation performed AutoDock simulations for as few as 1140 of the 64,000 α-CTx MII peptide mutants and could consistently identify a set of 10 peptides with an aggregated binding energy that was at least 98% of the aggregated binding energy of the 10 top peptides from the exhaustive AutoDock screening.

  13. Large-scale preparation of the homogeneous LolA–lipoprotein complex and efficient in vitro transfer of lipoproteins to the outer membrane in a LolB-dependent manner

    OpenAIRE

    Watanabe, Shoji; Oguchi, Yuki; Yokota, Naoko; Tokuda, Hajime

    2007-01-01

    An ATP-binding cassette transporter LolCDE complex of Escherichia coli releases lipoproteins destined to the outer membrane from the inner membrane as a complex with a periplasmic chaperone, LolA. Interaction of the LolA–lipoprotein complex with an outer membrane receptor, LolB, then causes localization of lipoproteins to the outer membrane. As far as examined, formation of the LolA–lipoprotein complex strictly depends on ATP hydrolysis by the LolCDE complex in the presence of LolA. It has be...

  14. Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

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    Felipe Romero-Saavedra

    Full Text Available Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens.We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72% between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm, and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm. These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens.Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier

  15. Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila

    Science.gov (United States)

    Ishikawa, Zachary

    2017-01-01

    The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis. PMID:28095410

  16. Kinetic studies of atherogenic lipoproteins in hemodialysis patients: do they tell us more about their pathology?

    Science.gov (United States)

    Kronenberg, Florian; Ikewaki, Katsunori; Schaefer, Juergen R; König, Paul; Dieplinger, Hans

    2007-01-01

    Patients with chronic kidney disease have one of the highest risks for atherosclerotic complications. Several large epidemiological studies described an opposite association of total and low density lipoprotein (LDL) cholesterol with cardiovascular complications and total mortality compared to the general population, a circumstance often called "reverse epidemiology." Many factors might contribute to this reversal such as interaction with malnutrition/inflammation, pronounced fluctuations of atherogenic lipoproteins during the course of renal disease, heterogeneity of lipoprotein particles with preponderance of remnant particles, and chemical modification of lipoproteins caused by the uremic environment. A vicious cycle has been suggested in uremia in which the decreased catabolism of atherogenic lipoproteins such as LDL, IDL and Lp(a) leads to their increased plasma residence time and further modification of these lipoproteins by oxidation, carbamylation, and glycation. Using stable isotope techniques, it has been shown recently that the plasma residence time of these particles is more than twice as long in hemodialysis patients as in nonuremic subjects. This reduced catabolism, however, is masked by the decreased production of LDL, resulting in near-normal plasma levels of LDL. The production rate of Lp(a) in hemodialysis patients is similar to that in controls which together with the doubled residence time results in elevated Lp(a) levels. An increased clearance of these altered lipoproteins via the scavenger receptors of macrophages leads to the transformation of macrophages into foam cells in the vascular wall and might contribute to the pronounced risk for cardiovascular complications of these patients. These observations suggest that the real danger of these particles is not reflected by the measured concentrations but by their metabolic qualities.

  17. EFFECTS OF EXERCISE TRAINING ON BLOOD LIPIDS AND LIPOPROTEINS IN CHILDREN AND ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    Kerstin Stoedefalke

    2007-09-01

    Full Text Available The following review aims to describe what is known about the effects of exercise training in children and adolescents on the following blood lipids and lipoproteins: total cholesterol (TC, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C, and triglycerides (TG. Only studies that described mode, frequency, duration and intensity of the exercise were included in the review. The results of the studies reviewed were equivocal. Clearly the effects of exercise training on the blood lipid and lipoprotein levels of normolipidemic children and adolescents are equivocal. Of the 14 studies reviewed, six observed a positive alteration in the blood lipid and lipoprotein profile, four of the studies observed no alteration in the blood lipid and lipoprotein profile and one study observed a negative effect on HDL-C but an overall improvement in the lipid and lipoprotein profile due to the decrease in the TC/HDL ratio. It appears that methodological problems present in the majority of the exercise training studies limits the ability to make a conclusive, evidence based statement regarding the effect exercise training has on blood lipid levels in normolipidemic children. Most of the research design flaws can be linked to one or more of the following: small numbers of subjects in each study, low or no representation of girls, inclusion of both boys and girls in the subject pool, inclusion of boys and girls at different maturational stages in the subject pool, exercise training regimes that do not adequately control for exercise intensity, exercise training regimes that do not last longer than 8 weeks and exercise training studies that do not have an adequate exercise volume to elicit a change. Ideally, future research should focus on longitudinal studies which examine the effects of exercise training from the primary school years through adulthood

  18. Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

    Science.gov (United States)

    Dantas, Simone Alves; Ficker, Elisabeth Salvatori; Vinagre, Carmen G. C.; Ianni, Barbara Maria; Maranhão, Raul Cavalcante; Mady, Charles

    2010-01-01

    INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [3H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m2] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h−1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower. PMID:20126342

  19. The impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a): Objectives and methods of a randomised controlled trial.

    Science.gov (United States)

    Khan, Tina Z; Pottle, Alison; Pennell, Dudley J; Barbir, Mahmoud S

    2015-05-01

    It is well established that Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor and predictor of major adverse cardiovascular events. Lipoprotein apheresis is currently the most effective approved treatment available, with minimal effect conferred by conventional lipid lowering agents. A growing body of evidence suggests that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although more prospective research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation is extremely challenging to manage. There is a significant unmet need to establish therapeutic options. Our goal is to determine the impact of lipoprotein apheresis on clinical parameters and symptoms of patients with refractory angina secondary to advanced coronary disease and raised Lp(a). Determining whether we should aggressively lower Lp(a) in such patients remains a very important question, which could potentially impact on the management of a large population. We will also gain insight into how this treatment works and the mechanisms via which Lp(a) increases cardiovascular risk. We are currently conducting a prospective, randomised controlled crossover study of patients with refractory angina and raised Lp(a), randomised to undergoing three months of weekly lipoprotein apheresis or sham apheresis. Patients will then crossover to the opposite study arm after a 1 month wash-out phase. We will assess myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised LDL and their antibodies, exercise capacity, angina and quality of life at the beginning and end of treatment, to determine the net true treatment effect on the above parameters. This is a novel area of research, as previous studies have not assessed the role of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in a prospective randomised controlled manner.

  20. 10 October 2013 - D. Braun First Deputy Minister for Regional Development, Czech Republic, P. Styczeń Deputy Minister of Transport, Construction and Maritime Economy, Republic of Poland and F. Palko State Secretary, Ministry of Transport, Construction and Regional Development, Slovak Republic visiting the LHC tunnel at Point 1 with Technology Department, Vacuum, Surfaces and Coatings Group Leader J. M. Jimenez and signing the Guest book with CERN Director-General R. Heuer

    CERN Multimedia

    Anna Pantelia

    2013-01-01

    10 October 2013 - D. Braun First Deputy Minister for Regional Development, Czech Republic, P. Styczeń Deputy Minister of Transport, Construction and Maritime Economy, Republic of Poland and F. Palko State Secretary, Ministry of Transport, Construction and Regional Development, Slovak Republic visiting the LHC tunnel at Point 1 with Technology Department, Vacuum, Surfaces and Coatings Group Leader J. M. Jimenez and signing the Guest book with CERN Director-General R. Heuer

  1. Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate

    Directory of Open Access Journals (Sweden)

    Alexis C. Frazier-Wood

    2014-08-01

    Full Text Available Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS associated several single nucleotide polymorphisms (SNPs with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs for fasting lipoprotein measures at baseline (pre-fenofibrate, and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004. Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001. Mixed linear models which controlled for age, sex, body mass index (BMI, smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004, however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.

  2. Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Takase, I.; Ishino, F.; Wachi, M.; Kamata, H.; Doi, M.; Asoh, S.; Matsuzawa, H.; Ohta, T.; Matsuhashi, M.

    1987-12-01

    The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of /sup 3/H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (M/sub r/ 35,615, rlpA lipoprotein) and 175 amino acids (M/sub r/ 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lioproteins may be important in duplication of the cells.

  3. The relationship between oxidized lipoprotein(a and carotid atherosclerosis in asymptomatic subjects: A comparison with native lipoprotein(a

    Directory of Open Access Journals (Sweden)

    Taniguchi Nobuyuki

    2011-10-01

    Full Text Available Abstract Background Oxidized lipoprotein(a (oxLp(a can be a more potent marker of atherogenesis than native Lp(a, although Lp(a is considered to be a risk factor for atherosclerotic diseases. Limited clinical data are available regarding the significance of oxLp(a in atherosclerotic manifestations. This study aimed to investigate the association between the serum oxLp(a and carotid artery intima-media thickness (CIMT, in comparison to the serum Lp(a levels, among asymptomatic subjects. Methods The atheroscrerosis-related variables including Lp(a and oxLp(a were measured in 136 cardiovascular disease-free subjects (61 males and 75 females, mean age of 64 years. The serum oxLp(a level was quantified using a sandwich ELISA system. The CIMT level was ultrasonographically measured on bilateral carotid arteries. Results The median level of Lp(a was 120 μmol/L, oxLp(a was 0.06 nmol/L, and CIMT was 0.7 mm, respectively. A simple correlation test showed that the CIMT was significantly and positively correlated with age, systolic blood pressure and oxLp(a (r = 0.208, P Conclusions These results suggest that oxLp(a may be more closely associated with accelerated carotid atherosclerosis, in comparison to Lp(a, in this population. This finding can be important for obtaining a better understanding of the different atherogenic roles played by oxLp(a in comparison to Lp(a.

  4. Amuvatinib has cytotoxic effects against NRAS-mutant melanoma but not BRAF-mutant melanoma.

    Science.gov (United States)

    Fedorenko, Inna V; Fang, Bin; Koomen, John M; Gibney, Geoffrey T; Smalley, Keiran S M

    2014-10-01

    Effective targeted therapy strategies are still lacking for the 15-20% of melanoma patients whose melanomas are driven by oncogenic NRAS. Here, we report on the NRAS-specific behavior of amuvatinib, a kinase inhibitor with activity against c-KIT, Axl, PDGFRα, and Rad51. An analysis of BRAF-mutant and NRAS-mutant melanoma cell lines showed the NRAS-mutant cohort to be enriched for targets of amuvatinib, including Axl, c-KIT, and the Axl ligand Gas6. Increasing concentrations of amuvatinib selectively inhibited the growth of NRAS-mutant, but not BRAF-mutant melanoma cell lines, an effect associated with induction of S-phase and G2/M-phase cell cycle arrest and induction of apoptosis. Mechanistically, amuvatinib was noted to either inhibit Axl, AKT, and MAPK signaling or Axl and AKT signaling and to induce a DNA damage response. In three-dimensional cell culture experiments, amuvatinib was cytotoxic against NRAS-mutant melanoma cell lines. Thus, we show for the first time that amuvatinib has proapoptotic activity against melanoma cell lines, with selectivity observed for those harboring oncogenic NRAS.

  5. Systemic Inflammatory Markers Are Closely Associated with Atherogenic Lipoprotein Subfractions in Patients Undergoing Coronary Angiography

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    Yan Zhang

    2015-01-01

    Full Text Available Objective. To investigate the relationship between inflammatory markers and atherogenic lipoprotein subfractions. Methods. We studied 520 eligible subjects who were not receiving any lipid-lowering therapy. The inflammatory markers including white blood cell (WBC count, high-sensitivity C-reactive protein (hs-CRP, fibrinogen, erythrocyte sedimentation rate (ESR, and D-dimer were measured. A multimarker inflammatory index was developed. Low-density lipoprotein (LDL and high-density lipoprotein (HDL separation processes were performed using Lipoprint System. Results. In age- and sex-adjusted analysis, several inflammatory markers (WBC count, hs-CRP, fibrinogen, and ESR were positively related to circulating non-HDL cholesterol and remnant cholesterol (p<0.05, all. Among lipoprotein subfractions, we observed a positive association of inflammatory markers with very low-density lipoprotein cholesterol, small LDL cholesterol, and LDL score (p<0.05, all. Meanwhile, a negative association was detected between inflammatory markers and mean LDL particle size (p<0.05 or large HDL cholesterol (p<0.05. Moreover, we found that the relationships between multimarker index quartiles and small LDL cholesterol, LDL score, and mean LDL particle size were slightly stronger in patients with CAD. Conclusions. Systemic inflammatory markers are positively correlated with small LDL cholesterol and LDL score while being negatively linked with mean LDL particle size and large HDL cholesterol, highlighting the potential contribution to increased cardiovascular risk.

  6. Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Lin; Liu, Yanzhu; Forte, Trudy M.; Chisholm, Jeffrey W.; Parks, John S.; Shachter, Neil S.

    2003-12-01

    We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.

  7. Vegetable oils affect the composition of lipoproteins in sea bream (Sparus aurata).

    Science.gov (United States)

    Caballero, Maria José; Torstensen, Bente E; Robaina, Lidia; Montero, Daniel; Izquierdo, Marisol

    2006-11-01

    The aim of the present study was to determine the influence of the dietary fatty acid profile on the lipoprotein composition in sea bream fed different vegetable oils. Six experimental diets were formulated combining fish oil with three vegetable oils (soybean, rapeseed, linseed) in order to obtain 60-80 % (w/w) fish-oil replacement. VLDL, LDL and HDL in plasma samples were obtained by sequential centrifugal flotation. The lipid class, protein content and fatty acid composition of each lipoprotein fraction were analysed. HDL was the predominant lipoprotein in sea bream plasma containing the highest proportion of protein (34 %) and phosphatidylcholine. LDL presented a high content of cholesterol, whereas triacylglycerol comprised a larger proportion of VLDL. The lipid class of the lipoprotein fractions was affected by the dietary vegetable oils. Thus, a high dietary inclusion of soyabean and linseed oil (80 %) increased the cholesterol in HDL and LDL in comparison to fish oil. Similarly, the triacylglycerol concentration of VLDL was increased in fish fed 80 % soyabean and linseed oils owing to the low n-3 highly unsaturated fatty acid content of these diets. Lipoprotein fatty acid composition easily responded to dietary fatty acid composition. VLDL was the fraction more affected by dietary fatty acid, followed by LDL and HDL. The n-3 highly unsaturated fatty acid content increased in the order VLDL less than LDL and less than HDL, regardless of dietary vegetable oils.

  8. Comparison of apoprotein B of low density lipoproteins of human interstitial fluid and plasma.

    Science.gov (United States)

    Hong, J L; Pflug, J; Reichl, D

    1984-08-15

    Virtually all apoprotein B (apoB)-containing lipoproteins of the peripheral interstitial fluid of subjects with primary lymphoedema float in the ultracentrifugal field in the density interval 1.019-1.063 g/ml; in this respect they are similar to plasma low-density lipoproteins (LDL). 2. Virtually all apo-B-containing lipoproteins of interstitial fluid migrate in the electrophoretic field with pre-beta mobility; in this respect they are similar to plasma very-low-density lipoproteins. 3. The apoB of lipoproteins of interstitial fluid does not differ in terms of Mr from apoB-100 of human plasma [Kane, Hardman & Paulus (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2465-2469] as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 4. Both apoB of interstitial fluid and plasma are heterogenous in terms of their charge as determined by isoelectric focusing of their complexes with the nonionic detergent Nonidet P40. ApoB of plasma LDL focuses between pH5.9 and 6.65, and that of interstitial fluid LDL between pH 5.9 and 6.1. Thus the overall charge of apoB of interstitial fluid is more negative than that of its plasma LDL counterpart.

  9. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Shou-Kui Xiang

    2012-01-01

    Full Text Available Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS. Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2, total testosterone (T, fasting glucose (FBG, fasting insulin (FINS, serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein (HDL-C, and low-density lipoprotein (LDL-C levels were checked, and then TG/HDL-C ratio, TC/HDL-C, ratio and LDL-C/HDL-C ratio were calculated. The homeostasis model assessment of insulin resistance (HOMA-IR was used to calculate the insulin resistance. Results. All lipoprotein ratios were significantly higher in PCOS patients as compared to healthy controls (<0.05. TG/HDL-C ratio, TC/HDL-C ratio, and LDL-C/HDL-C ratio were significantly correlated with HOMA-IR (<0.05. The ROC curve demonstrated that TC/HDL-C ratio had higher sensitivity and specificity in diagnosing PCOS with insulin resistance. Conclusion. This study demonstrates that serum lipoprotein ratio significantly correlates with insulin resistance and can be used as the marker of insulin resistance in PCOS patients.

  10. Circulating lipoproteins are a crucial component of host defense against invasive Salmonella typhimurium infection.

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    Mihai G Netea

    Full Text Available BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS, thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/- mice, with a 7-fold increase in LDL, are resistant against infection with Salmonella typhimurium (survival 100% vs 5%, p<0.001, and 100 to 1000-fold lower bacterial burden in the organs, compared with LDLR+/+ mice. Protection was not due to differences in cytokine production, phagocytosis, and killing of Salmonella organisms. The differences were caused by the excess of lipoproteins, as hyperlipoproteinemic ApoE-/- mice were also highly resistant to Salmonella infection. Lipoproteins protect against infection by interfering with the binding of Salmonella to host cells, and preventing organ invasion. This leads to an altered biodistribution of the microorganisms during the first hours of infection: after intravenous injection of Salmonella into LDLR+/+ mice, the bacteria invaded the liver and spleen within 30 minutes of infection. In contrast, in LDLR-/- mice, Salmonella remained constrained to the circulation from where they were efficiently cleared, with decreased organ invasion. CONCLUSIONS: plasma lipoproteins are a potent host defense mechanism against invasive Salmonella infection, by blocking adhesion of Salmonella to the host cells and subsequent tissue invasion.

  11. Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance.

    Science.gov (United States)

    Couture, Patrick; Tremblay, André J; Kelly, Isabelle; Lemelin, Valéry; Droit, Arnaud; Lamarche, Benoît

    2014-01-01

    Insulin resistance (IR) is associated with elevated plasma levels of triglyceride-rich lipoproteins (TRLs) of intestinal origin. However, the mechanisms underlying the overaccumulation of apolipoprotein (apo)B-48-containing TRLs in individuals with IR are not yet fully understood. This study examined the relationships between apoB-48-containing TRL kinetics and the expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism in 14 obese nondiabetic men with IR compared with 10 insulin-sensitive (IS) men matched for waist circumference. The in vivo kinetics of TRL apoB-48 were assessed using a primed-constant infusion of L-[5,5,5-D₃]leucine for 12 h with the participants in a constantly fed state. The expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism was assessed by performing real-time PCR quantification and LC-MS/MS on duodenal biopsy specimens. The TRL apoB-48 pool size and production rate were 102% (P < 0.0001) and 87% (P = 0.01) greater, respectively, in the men with IR versus the IS men. On the other hand, intestinal mRNA levels of sterol regulatory element binding factor-2, hepatocyte nuclear factor-4α, and microsomal triglyceride transfer protein were significantly lower in the men with IR than in the IS men. These data indicate that IR is associated with intestinal overproduction of lipoproteins and significant downregulation of key intestinal genes involved in lipid/lipoprotein metabolism.

  12. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    Science.gov (United States)

    Meeusen, Jeffrey W; Snozek, Christine L; Baumann, Nikola A; Jaffe, Allan S; Saenger, Amy K

    2015-08-15

    Aggressive low-density lipoprotein cholesterol (LDL-C)-lowering strategies are recommended for prevention of cardiovascular events in high-risk populations. Guidelines recommend a 30% to 50% reduction in at-risk patients even when LDL-C concentrations are between 70 and 130 mg/dl (1.8 to 3.4 mmol/L). However, calculation of LDL-C by the Friedewald equation is the primary laboratory method for routine LDL-C measurement. We compared the accuracy and reproducibility of calculated LDL-C <130 mg/dl (3.4 mmol/L) to LDL-C measured by β quantification (considered the gold standard method) in 15,917 patients with fasting triglyceride concentrations <400 mg/dl (4.5 mmol/L). Both variation and bias of calculated LDL-C increased at lower values of measured LDL-C. The 95% confidence intervals for a calculated LDL-C of 70 mg/dl (1.8 mmol/L) and 30 mg/dl (0.8 mmol/L) were 60 to 86 mg/dl (1.6 to 2.2 mmol/L) and 24 to 60 mg/dl (0.6 to 1.6 mmol/L), respectively. Previous recommendations have emphasized the requirement for a fasting sample with triglycerides <400 mg/dl (4.5 mmol/L) to calculate LDL-C by the Friedewald equation. However, no recommendations have addressed the appropriate lower reportable limit for calculated LDL-C. In conclusion, calculated LDL-C <30 mg/dl (0.8 mmol/L) should not be reported because of significant deviation from the gold standard measured LDL-C results, and caution is advised when using calculated LDL-CF values <70 mg/dl (1.8 mmol/L) to make treatment decisions.

  13. Human endothelial progenitor cells internalize high-density lipoprotein.

    Science.gov (United States)

    Srisen, Kaemisa; Röhrl, Clemens; Meisslitzer-Ruppitsch, Claudia; Ranftler, Carmen; Ellinger, Adolf; Pavelka, Margit; Neumüller, Josef

    2013-01-01

    Endothelial progenitor cells (EPCs) originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL), and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate), cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal intraellular

  14. Human endothelial progenitor cells internalize high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Kaemisa Srisen

    Full Text Available Endothelial progenitor cells (EPCs originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL, and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate, cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal

  15. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    Science.gov (United States)

    Ossoli, Alice; Neufeld, Edward B; Thacker, Seth G; Vaisman, Boris; Pryor, Milton; Freeman, Lita A; Brantner, Christine A; Baranova, Irina; Francone, Nicolás O; Demosky, Stephen J; Vitali, Cecilia; Locatelli, Monica; Abbate, Mauro; Zoja, Carlamaria; Franceschini, Guido; Calabresi, Laura; Remaley, Alan T

    2016-01-01

    Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.

  16. Targeting ESR1-Mutant Breast Cancer

    Science.gov (United States)

    2015-09-01

    disease-free survival, the majority of breast cancer patients will present recurrent antiestrogen resistant metastatic lesions following prolonged...exposure to these therapies. By investigating how these lesions become resistant to antiestrogen while maintaining expression of ERα, we found...Retreat. Invited oral presentation. C) Other products Nothing to report. Targeting  ESR1-­‐Mutant  Breast  Cancer   W81XWH-­‐14-­‐1-­‐0360

  17. Characterization of a Legionella micdadei mip mutant

    DEFF Research Database (Denmark)

    O'Connell, W A; Bangsborg, Jette Marie; Cianciotto, N P

    1995-01-01

    The pathogenesis of Legionella micdadei is dependent upon its ability to infect alveolar phagocytes. To better understand the basis of intracellular infection by this organism, we examined the importance of its Mip surface protein. In Legionella pneumophila, Mip promotes infection of both human m...... into the phagocyte. Similarly, the mutant was less able to parasitize Hartmannella amoebae. Taken together, these data argue that Mip specifically potentiates intracellular growth by L. micdadei....

  18. Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease

    DEFF Research Database (Denmark)

    Holme, Ingar; Cater, Nilo B; Faergeman, Ole;

    2008-01-01

    the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). FINDINGS: Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less...... predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. INTERPRETATION: The on-treatment level of apoB/apoA-1...

  19. Method of assessing a lipid-related health risk based on ion mobility analysis of lipoproteins

    Science.gov (United States)

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-12-14

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  20. Determining the risk of cardiovascular disease using ion mobility of lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-05-11

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  1. Progress of cardioprotective effects of high density lipoprotein: function and mechanism

    Directory of Open Access Journals (Sweden)

    Hai-ge SUN

    2015-01-01

    Full Text Available The high density lipoprotein (HDL in human plasma is a heterogeneous lipoprotein consisting of roughly equal contents of lipid and protein in roughly equal content, and it consists of several subtypes. HDL possesses several well-documented functions, including anti-atherosclerosis by promoting reverse cholesterol transport, inhibiting the oxidative modification of low density lipoproteins (LDLs, inhibiting vascular inflammation, preventing thrombosis and apoptosis, and promoting endothelial repair. Recently, more cardiovascular protective functions of HDL have been found, mainly including the ability of suppressing immune inflammatory reaction, inhibiting the proliferation of hematopoietic stem cells, and regulating the plasma glucose level. It is of great importance to understand how different HDL subtypes contribute to the potentially cardioprotective functions. DOI: 10.11855/j.issn.0577-7402.2014.11.13

  2. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

    Science.gov (United States)

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

  3. Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Kamstrup, Pia Rørbæk; Nordestgaard, Børge

    2013-01-01

    BACKGROUND: Low concentrations of lipoprotein(a) in plasma are associated with increased risk of type 2 diabetes, but whether this association is causal is unclear. Variations in the LPA gene affect lipoprotein(a) isoform size and concentrations in plasma. We therefore did a Mendelian randomisation...... study to investigate whether large isoform size, low concentrations in plasma, or both, are causally associated with type 2 diabetes. METHODS: We assessed data for adults from the Danish general population enrolled in the Copenhagen City Heart Study and the Copenhagen General Population Study......, with and without type 2 diabetes. Eligible participants had data for lipoprotein(a) concentrations in plasma, LPA kringle IV type 2 (KIV-2) sums of repeats (affecting both isoform size and plasma concentrations), and carrier status for the LPA single-nucleotide polymorphism rs10455872 (mainly affecting...

  4. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro

    DEFF Research Database (Denmark)

    Niemeier, A; Willnow, T; Dieplinger, H;

    1999-01-01

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein of unknown physiological function. The mechanism of Lp(a) atherogenicity as well as its catabolic pathways are only incompletely understood at present. In this report, we show that the low density lipoprotein receptor (LDLR) gene family member...... megalin/glycoprotein (gp) 330 is capable of binding and mediating the cellular uptake and degradation of Lp(a) in vitro. A mouse embryonic yolk sac cell line with native expression of megalin/gp330 but genetically deficient in LDLR-related protein (LRP) and a control cell line carrying a double knockout...... unlabeled Lp(a) and LDL suggested that Lp(a) uptake is mediated at least partially by apolipoprotein B100. Binding and uptake of DiI-Lp(a) resulted in strong signals on megalin/gp330-expressing cells versus background only on control cells. In addition, we show that purified megalin/gp330, immobilized...

  5. Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?

    DEFF Research Database (Denmark)

    Dahlbäck, B; Nielsen, Lars Bo

    2009-01-01

    M retains its signal peptide, which serves as a hydrophobic anchor to the lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma (1 microM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting......Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ss-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. Apo......; possible mechanisms include increased formation of pre-ss HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties....

  6. Lipoprotein apheresis and new therapies for severe familial hypercholesterolemia in adults and children.

    Science.gov (United States)

    Page, Michael M; Bell, Damon A; Hooper, Amanda J; Watts, Gerald F; Burnett, John R

    2014-06-01

    Familial hypercholesterolemia (FH), the most common and severe monogenic form of hypercholesterolemia, is an autosomal co-dominant disease characterized by an increased plasma low density lipoprotein (LDL)-cholesterol concentration and premature coronary heart disease (CHD). The clinical phenotype depends on the gene involved and severity of mutation (or mutations) present. Patients with homozygous or compound heterozygous FH have severe hypercholesterolemia (LDL-cholesterol >13 mmol/L) due to a gene dosing effect and without treatment have accelerated atherosclerotic CHD from birth, and frequently die of CHD before age 30. Cholesterol-lowering therapies have been shown to reduce both mortality and major adverse cardiovascular events in individuals with FH. Lipoprotein apheresis concomitant with lipid-lowering therapy is the treatment of choice for homozygous FH. This article describes the rationale and role of lipoprotein apheresis in the treatment of severe FH and outlines the recent advances in new pharmacotherapies for this condition.

  7. Triglycerides and high-density lipoprotein cholesterol are associated with insulinemia in adolescents

    Directory of Open Access Journals (Sweden)

    Ramírez-López Guadalupe

    2006-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the association between lipids and insulin concentration in adolescents. MATERIAL AND METHODS: A cross-sectional study of 350 adolescents aged 14-19 years old from a public high school in Guadalajara, in the state of Jalisco, Mexico, was conducted. Fasting insulin concentration was determined using microparticle enzyme immunoassay; total cholesterol and triglycerides were detected by standard enzymatic procedures; and low- and high-density lipoproteins were found using standard precipitation methods. Statistical analysis included linear multivariate regression. RESULTS: Serum triglycerides were associated positively with insulin fasting (beta= 0.003, p= 0.0001 and high-density lipoprotein cholesterol was negatively associated with insulin fasting in male adolescents 18-19 years old (beta= -0.03, p= 0.012. CONCLUSIONS: The relationships between triglycerides and insulin and between high-density lipoprotein cholesterol and insulin are already present in adolescence.

  8. The role of lipoprotein processing by signal peptidase II in the Gram-positive eubacterium Bacillus subtilis : Signal peptidase II is required for the efficient secretion of alpha-amylase, a non-lipoprotein

    NARCIS (Netherlands)

    Tjalsma, H; Kontinen, VP; Pragai, Z; Meima, R; Venema, G; Bron, S; Sarvas, M; van Dijl, JM

    1999-01-01

    Computer-assisted analyses indicate that Bacillus subtilis contains approximately 300 genes for exported proteins with an amino-terminal signal peptide. About 114 of these are lipoproteins, which are retained in the cytoplasmic membrane. We have investigated the importance of lipoprotein processing

  9. Mice with chimeric livers are an improved model for human lipoprotein metabolism.

    Directory of Open Access Journals (Sweden)

    Ewa C S Ellis

    Full Text Available OBJECTIVE: Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. DESIGN: FRG [ F ah(-/- R ag2(-/-Il2r g (-/-] mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. RESULTS: Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA. Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. CONCLUSION: Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

  10. Lipids, lipoproteins, fibrinogen and fibrinolytic activity in angiographically assessed coronary heart disease.

    Science.gov (United States)

    Lipinska, I; Gurewich, V; Meriam, C M; Kosowsky, B D; Ramaswamy, K; Philbin, E; Losordo, D

    1987-01-01

    Plasma lipids, lipoproteins, fibrinogen and fibrinolytic activity (FA) were measured in 202 consecutive patients undergoing coronary angiography. Twenty-one patients, 13 men and 8 women with a mean age of 52.8 years and 56.7 years respectively, were found to be angiographically free of coronary artery disease (CAD) and served as the principal control group. Since this group contained a disproportionate number of subjects with risk factors such as family history, hypertension and smoking, a second control group of clinically healthy subjects selected for age was also tested. Their laboratory results were not used in the statistical calculations. The group with angiographic CAD consisted of 130 men (mean age 57.6 years) and 51 women (mean age 61.5 years). Abnormal angiograms were graded according to the number of major vessels with more than 50% stenosis involved. The laboratory variables which were significantly (p less than .01-.001) associated with the presence of CAD were: High density lipoprotein (HDL) when determined by polyacrylamide gel electrophoresis (PAGE) and expressed as a percentage of total lipoproteins rather than concentration, presence of Intermediate Density Lipoprotein (IDL), percent of Very Low Density Lipoprotein (VLDL), fibrinogen concentration and FA. The HDL2 subfraction was significantly inversely correlated only in women. The total plasma cholesterol was normal and virtually identical in both groups. Within the CAD group, only two of the laboratory results were significantly correlated with the extent of disease. By univariate analysis, the FA showed the closest association with the score for severity of CAD (p less than .001) followed by the presence of IDL (p less than .01). In conclusion, lipoprotein analysis by a method which measures not only HDL, but also LDL, VLDL and IDL, together with the determination of fibrinogen and FA provides information useful in the identification of individuals at risk for CAD.

  11. Insights on the structure and stability of Licanantase: a trimeric acid-stable coiled-coil lipoprotein from Acidithiobacillus thiooxidans

    Directory of Open Access Journals (Sweden)

    Fernando Abarca

    2014-08-01

    Full Text Available Licanantase (Lic is the major component of the secretome of Acidithiobacillus thiooxidans when grown in elemental sulphur. When used as an additive, Lic improves copper recovery from bioleaching processes. However, this recovery enhancement is not fully understood. In this context, our aim is to predict the 3D structure of Lic, to shed light on its structure-function relationships. Bioinformatics analyses on the amino acid sequence of Lic showed a great similarity with Lpp, an Escherichia coli Lipoprotein that can form stable trimers in solution. Lic and Lpp share the secretion motif, intracellular processing and alpha helix structure, as well as the distribution of hydrophobic residues in heptads forming a hydrophobic core, typical of coiled-coil structures. Cross-linking experiments showed the presence of Lic trimers, supporting our predictions. Taking the in vitro and in silico evidence as a whole, we propose that the most probable structure for Lic is a trimeric coiled-coil. According to this prediction, a suitable model for Lic was produced using the de novo algorithm “Rosetta Fold-and-Dock”. To assess the structural stability of our model, Molecular Dynamics (MD and Replica Exchange MD simulations were performed using the structure of Lpp and a 14-alanine Lpp mutant as controls, at both acidic and neutral pH. Our results suggest that Lic was the most stable structure among the studied proteins in both pH conditions. This increased stability can be explained by a higher number of both intermonomer hydrophobic contacts and hydrogen bonds, key elements for the stability of Lic’s secondary and tertiary structure.

  12. Insights on the structure and stability of Licanantase: a trimeric acid-stable coiled-coil lipoprotein from Acidithiobacillus thiooxidans.

    Science.gov (United States)

    Abarca, Fernando; Gutierrez-Maldonado, Sebastian E; Parada, Pilar; Martinez, Patricio; Maass, Alejandro; Perez-Acle, Tomas

    2014-01-01

    Licanantase (Lic) is the major component of the secretome of Acidithiobacillus thiooxidans when grown in elemental sulphur. When used as an additive, Lic improves copper recovery from bioleaching processes. However, this recovery enhancement is not fully understood. In this context, our aim is to predict the 3D structure of Lic, to shed light on its structure-function relationships. Bioinformatics analyses on the amino acid sequence of Lic showed a great similarity with Lpp, an Escherichia coli Lipoprotein that can form stable trimers in solution. Lic and Lpp share the secretion motif, intracellular processing and alpha helix structure, as well as the distribution of hydrophobic residues in heptads forming a hydrophobic core, typical of coiled-coil structures. Cross-linking experiments showed the presence of Lic trimers, supporting our predictions. Taking the in vitro and in silico evidence as a whole, we propose that the most probable structure for Lic is a trimeric coiled-coil. According to this prediction, a suitable model for Lic was produced using the de novo algorithm "Rosetta Fold-and-Dock". To assess the structural stability of our model, Molecular Dynamics (MD) and Replica Exchange MD simulations were performed using the structure of Lpp and a 14-alanine Lpp mutant as controls, at both acidic and neutral pH. Our results suggest that Lic was the most stable structure among the studied proteins in both pH conditions. This increased stability can be explained by a higher number of both intermonomer hydrophobic contacts and hydrogen bonds, key elements for the stability of Lic's secondary and tertiary structure.

  13. Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia.

    Science.gov (United States)

    Katzel, L I; Busby-Whitehead, M J; Rogus, E M; Krauss, R M; Goldberg, A P

    1994-02-01

    Healthy older (64 +/- 1 years, mean +/- SEM) athletic (maximal oxygen consumption [VO2max] > 40 mL/kg/min) normocholesterolemic men with no prior history of coronary artery disease (CAD) were recruited for cardiovascular and metabolic studies. Thirty-three percent had asymptomatic exercise-induced ST segment depression on their exercise electrocardiogram (ECG), consistent with silent myocardial ischemia (SI). We hypothesized that abnormalities in high-density lipoprotein (HDL) and postprandial triglyceride (TG) metabolism may increase their risk for CAD. Compared with 12 nonischemic controls of comparable age, percent body fat, and VO2max, the 13 men with SI had decreased fasting HDL cholesterol ([HDL-C] 41 +/- 2 v 50 +/- 2 mg/dL, P postprandial plasma TG, chylomicron-TG, and very-low-density lipoprotein (VLDL)-TG levels and postprandial areas were higher in men with SI (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Transvascular low-density lipoprotein transport in patients with diabetes mellitus (type 2)

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo;

    2002-01-01

    accumulation and, thus, atherosclerosis. METHODS AND RESULTS: We developed an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 16 patients with maturity-onset diabetes (type 2) and 29 healthy control subjects. Autologous 131I-labeled LDL...... plasma insulin levels in diabetic patients. CONCLUSIONS: Transvascular LDL transport may be increased in patients with type 2 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with diabetes, possibly explaining the accelerated development of atherosclerosis....... in patients with diabetes and control subjects, respectively (P2.5%/h and 5.3+/-1.6%/h (P

  15. Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema

    DEFF Research Database (Denmark)

    Staurenghi, Giovanni; Ye, Li; Magee, Mindy H;

    2015-01-01

    PURPOSE: To investigate the potential of lipoprotein-associated phospholipase A2 inhibition as a novel mechanism to reduce edema and improve vision in center-involved diabetic macular edema (DME). DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled phase IIa study...... (AEs) and nonocular AEs were similar between treatment groups. CONCLUSIONS: Once-daily oral darapladib administered for 3 months demonstrated modest improvements in vision and macular edema that warrant additional investigation of this novel lipoprotein-associated phospholipase A2 inhibitory mechanism...

  16. Electrophoretic demonstration of glycoproteins, lipoproteins, and phosphoproteins in human and bovine enamel

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Bøg-Hansen, T C;

    1990-01-01

    Enamel proteins from fully mineralized human molars and from bovine tooth germs were separated by electrophoresis. The gels were stained for detection of glycoproteins, lipoproteins, and phosphoproteins. Glycoproteins were shown by periodic acid-Schiff staining and lectin blotting. In mature human...... enamel a number of high molecular weight proteins could be demonstrated after ethylenediaminetetra-acetic acid demineralization and subsequent Triton X-100 extraction. These proteins are suggested to be lipoproteins. Phosphoproteins could only be visualized in enamel matrix from the tooth germs....

  17. Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

    Science.gov (United States)

    Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

    2016-07-27

    Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

  18. Relationship between two common lipoprotein lipase variants and the metabolic syndrome and its individual components

    DEFF Research Database (Denmark)

    Vishram, Julie K. K.; Hansen, Tine W.; Torp-Pedersen, Christian

    2016-01-01

    BACKGROUND: Common lipoprotein lipase (LPL) variants are important determinants of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol (C) concentrations. High TG/low HDL-C tend to cluster with hypertension, glucose intolerance, and abdominal obesity and comprise the metabolic...... syndrome (MetS). The role of LPL variants as a cause of MetS is unclear. This study investigated the relationship between two common LPL variants and the presence of MetS and its individual components. METHODS: Cross-sectional study, including 2348 Danish women (50.7%) and men, age 41-72 years, without...

  19. A novel intrinsically disordered outer membrane lipoprotein of Aggregatibacter actinomycetemcomitans binds various cytokines and plays a role in biofilm response to interleukin-1β and interleukin-8.

    Science.gov (United States)

    Ahlstrand, Tuuli; Tuominen, Heidi; Beklen, Arzu; Torittu, Annamari; Oscarsson, Jan; Sormunen, Raija; Pöllänen, Marja T; Permi, Perttu; Ihalin, Riikka

    2017-02-17

    Intrinsically disordered proteins (IDPs) do not have a well-defined and stable 3-dimensional fold. Some IDPs can function as either transient or permanent binders of other proteins and may interact with an array of ligands by adopting different conformations. A novel outer membrane lipoprotein, bacterial interleukin receptor I (BilRI) of the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans binds a key gatekeeper proinflammatory cytokine interleukin (IL)-1β. Because the amino acid sequence of the novel lipoprotein resembles that of fibrinogen binder A of Haemophilus ducreyi, BilRI could have the potential to bind other proteins, such as host matrix proteins. However, from the tested host matrix proteins, BilRI interacted with neither collagen nor fibrinogen. Instead, the recombinant non-lipidated BilRI, which was intrinsically disordered, bound various pro/anti-inflammatory cytokines, such as IL-8, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Moreover, BilRI played a role in the in vitro sensing of IL-1β and IL-8 because low concentrations of cytokines did not decrease the amount of extracellular DNA in the matrix of bilRI(-) mutant biofilm as they did in the matrix of wild-type biofilm when the biofilms were exposed to recombinant cytokines for 22 hours. BilRI played a role in the internalization of IL-1β in the gingival model system but did not affect either IL-8 or IL-6 uptake. However, bilRI deletion did not entirely prevent IL-1β internalization, and the binding of cytokines to BilRI was relatively weak. Thus, BilRI might sequester cytokines on the surface of A. actinomycetemcomitans to facilitate the internalization process in low local cytokine concentrations.

  20. A novel missense mutation in the C-terminal domain of lipoprotein lipase (Glu410-->Val) leads to enzyme inactivation and familial chylomicronemia.

    Science.gov (United States)

    Previato, L; Guardamagna, O; Dugi, K A; Ronan, R; Talley, G D; Santamarina-Fojo, S; Brewer, H B

    1994-09-01

    Lipoprotein lipase (LPL) is a complex enzyme consisting of multiple functional domains essential for the initial hydrolysis of triglycerides present in plasma lipoproteins. Previous studies have localized the catalytic domain of LPL, responsible for the hydrolytic function of the enzyme, to the N-terminus whereas the C-terminal end may play a role in lipid and heparin binding. To date, most described missense mutations resulting in a nonfunctional LPL have been located in the N-terminal region of the enzyme. In this manuscript we describe the defect in the LPL gene of a patient with triglycerides ranging from normal to 12,000 mg/dl, low LPL mass, and no LPL activity in post-heparin plasma. Sequencing of patient PCR-amplified DNA identified two separate mutations in the C-terminal domain of LPL: an A-->T transversion at nucleotide 1484 resulting in a Glu410-->Val substitution and a C-->G mutation at position 1595 that introduces a premature stop codon at position 447. Digestion with MaeIII and MnII established that the patient is a true homozygote for both mutations. In order to investigate the functional significance of these defects, mutant enzymes containing either the Val410 or the Ter447 mutations as well as both Val410 and Ter447, were expressed in vitro. Compared to the wild-type enzyme, LPL447 demonstrated a moderate reduction of specific activity using triolein (70% of normal) and tributyrin (74% of normal) substrates, while LPL410 had a significant (11% and 23% of normal) reduction of the normal lipase and esterase specific activities, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Serum apolipoprotein(a) levels and its effect on the measured values of low density lipoprotein cholesterol.

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    Serum low density lipoprotein cholesterl (LDL-C) and lipoprotein(a)[Lp(a)]levels were analyzed in 1032 sequential cases on routine physical check up, with special attention to the effect of Lp(a) on the LDL-C values. Since the determination of LDL-C by various

  2. Effects of aerobic exercise, diet, or both on lipids and lipoproteins in adults: a meta-analysis

    Science.gov (United States)

    BACKGROUND: Studies addressing the effects of aerobic exercise (E), diet (D), or both (ED) on lipids and lipoproteins have led to conflicting results. OBJECTIVE: Determine the effects of E, D, and ED on lipids and lipoproteins. METHODS: Using the aggregate data meta-analytic approach, studies were ...

  3. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically defined disease in post-menopausal women

    Science.gov (United States)

    The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women. Plasma HDL subpopulation concentrations, quantified by 2-dimensional gel electrophoresis...

  4. Surface-associated lipoprotein PpmA of Streptococcus pneumoniae is involved in colonization in a strain-specific manner.

    NARCIS (Netherlands)

    Cron, L.E.; Bootsma, H.J.; Noske, N.; Burghout, P.J.; Hammerschmidt, S.; Hermans, P.W.M.

    2009-01-01

    Streptococcus pneumoniae produces two surface-associated lipoproteins that share homology with two distinct families of peptidyl-prolyl isomerases (PPIases), the streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A (PpmA). Previously, we have demonstrated that

  5. Effects of saturated, mono-, and polyunsaturated fatty acids on the secretion of apo B containing lipoproteins by Caco-2 cells

    NARCIS (Netherlands)

    van Greevenbroek, M.M.J.; van Meer, G.; Erkelens, D.W.; de Bruin, T.W.A.

    1996-01-01

    We studied the effects of addition of physiological concentrations (0.5 mM) of fatty acids i.e., palmitic (16:0), stearic (18:0), oleic (18:1) and linoleic acid (18:2) on lipoprotein secretion by polarized Caco-2 cells. With saturated fatty acids, secreted lipoproteins were at IDL/LDL density, 1.009

  6. Plasma Lipoprotein-associated Phospholipase A(2) Is Inversely Correlated with Proprotein Convertase Subtilisin-kexin Type 9

    NARCIS (Netherlands)

    Constantinides, Alexander; Kappelle, Paul J.W.H.; Lambert, Gilles; Dullaart, Robin P. F.

    2012-01-01

    Background and Aims. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proatherogenic phospholipase A(2), which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating L

  7. Elevated plasma cholesteryl ester transfer in NIDDM : relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

    NARCIS (Netherlands)

    Riemens, S; van Tol, A; Sluiter, W; Dullaart, R

    1998-01-01

    Lecithin:cholesteryl acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from high density lipoproteins (HDL) towards very low and low density lipoproteins (VLDL + LDL). Phospholip

  8. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

    DEFF Research Database (Denmark)

    Kjølby, Mads Fuglsang; Andersen, Olav Michael; Breiderhoff, Tilman

    2010-01-01

    receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion...

  9. [The alternative view on diagnostic of hyperlipoproteinemia, cholesterol lipoproteins of low density and effect of statins: a lecture].

    Science.gov (United States)

    Tupoleva, T A; Tikhomirov, D S; Grumbkova, L O; Ignatova, E N; Romanova, T Iu; Filatov, F P; Garanzha, T A

    2015-01-01

    The effect of statins occur in several stages: 1) inhibition in hepatocytes of synthesis of functionally specific pool of spirit cholesterol, polar mono-layer of lipoproteins of very low density; 2) activation of hydrolysis of triglycerides in lipoproteins of very low density, formation of apoE/B-100-ligand and absorption of lipoproteins of very low density by insulin-depended cells; 3) decreasing of content of and spirit cholesterol-lipoproteins of very low density in blood plasma; 4) activation of hydrolysis of triglycerides in lipoproteins of low density, formation of apoB-100-ligand and absorption of lipoproteins of low density by insulin-independent cells; 5) decreasing of level of and increasing of content of lipoproteins of high density. During first weeks of effect of statins occurs decreasing of concentration of triglycerides and unesterified spirit cholesterol-lipoproteins of very low density in blood plasma. Then, slower and more durational decreasing of level of spirit cholesterol-lipoproteins of low density occurs. The value of spirit cholesterol-lipoproteins of low density is primarily determined by content of palmitic saturated fatty acid in food, its endogenous synthesis from glucose and concentration of palmitic triglycerides and lipoproteins of very low density of the same name in blood plasma. The effect of preparations is biologically valid and corresponds to alternative hypolipidemic preparations. All these preparations have an effect following a common algorithm: they activate, using different mechanisms, receptor absorption of lipoproteins of very low density or lipoproteins of low density by cells. The level of spirit cholesterol-lipoproteins of low density in full measure depends on content of triglycerides in blood. The concentration of spirit cholesterol in blood plasma has a reliable diagnostic significance only under physiological content of triglycerides. The main criterion of diagnostic and control of hypolipidemic therapy

  10. Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

    Directory of Open Access Journals (Sweden)

    Thomas F. Baumert

    2013-05-01

    Full Text Available Hepatitis C virus (HCV is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects.

  11. Characterisation of cuticular mutants in Arabidopsis thaliana

    OpenAIRE

    Faust, Andrea

    2006-01-01

    Plants are protected by the extracellular cuticle, which is made up of cutin, cutan and waxes. The cutin composition of a variety of plants has been known and models of the biosynthesis of cutin monomers exist but not many enzymes have been identified. It is generally accepted that a defect in the cuticle leads to an organ fusion phenotype. In the model plant A. thaliana many fusion mutants have been identified but the identification of genes involved have not lead to a complete picture of th...

  12. Model of mouth-to-mouth transfer of bacterial lipoproteins through inner membrane LolC, periplasmic LolA, and outer membrane LolB

    OpenAIRE

    Okuda, Suguru; Tokuda, Hajime

    2009-01-01

    Outer membrane-specific lipoproteins in Escherichia coli are released from the inner membrane by an ATP-binding cassette transporter, the LolCDE complex, which causes the formation of a soluble complex with a periplasmic molecular chaperone, LolA. LolA then transports lipoproteins to the outer membrane where an outer membrane receptor, LolB, incorporates lipoproteins into the outer membrane. The molecular mechanisms underlying the Lol-dependent lipoprotein sorting have been clarified in detai...

  13. Low-density lipoprotein receptor-related protein-1 facilitates heme scavenging after intracerebral hemorrhage in mice.

    Science.gov (United States)

    Wang, Gaiqing; Manaenko, Anatol; Shao, Anwen; Ou, Yibo; Yang, Peng; Budbazar, Enkhjargal; Nowrangi, Derek; Zhang, John H; Tang, Jiping

    2016-06-17

    Heme-degradation after erythrocyte lysis plays an important role in the pathophysiology of intracerebral hemorrhage. Low-density lipoprotein receptor-related protein-1 is a receptor expressed predominately at the neurovascular interface, which facilitates the clearance of the hemopexin and heme complex. In the present study, we investigated the role of low-density lipoprotein receptor-related protein-1 in heme removal and neuroprotection in a mouse model of intracerebral hemorrhage. Endogenous low-density lipoprotein receptor-related protein-1 and hemopexin were increased in ipsilateral brain after intracerebral hemorrhage, accompanied by increased hemoglobin levels, brain water content, blood-brain barrier permeability and neurological deficits. Exogenous human recombinant low-density lipoprotein receptor-related protein-1 protein reduced hematoma volume, brain water content surrounding hematoma, blood-brain barrier permeability and improved neurological function three days after intracerebral hemorrhage. The expression of malondialdehyde, fluoro-Jade C positive cells and cleaved caspase 3 was increased three days after intracerebral hemorrhage in the ipsilateral brain tissues and decreased with recombinant low-density lipoprotein receptor-related protein-1. Intracerebral hemorrhage decreased and recombinant low-density lipoprotein receptor-related protein-1 increased the levels of superoxide dismutase 1. Low-density lipoprotein receptor-related protein-1 siRNA reduced the effect of human recombinant low-density lipoprotein receptor-related protein-1 on all outcomes measured. Collectively, our findings suggest that low-density lipoprotein receptor-related protein-1 contributed to heme clearance and blood-brain barrier protection after intracerebral hemorrhage. The use of low-density lipoprotein receptor-related protein-1 as supplement provides a novel approach to ameliorating intracerebral hemorrhage brain injury via its pleiotropic neuroprotective effects.

  14. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

    Institute of Scientific and Technical Information of China (English)

    El(z)bieta KIMAK; Magdalena HA(L)ABI(S); Iwona BARANOWICZ-GA SZCZYK; Janusz SOLSKI; Andrzej KSIA(Z)EK

    2011-01-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle,oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy.HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C,apoA-Ⅰ/apoB, HDL-C/apoA-Ⅰ, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre

  15. Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients.

    Science.gov (United States)

    Kimak, Elżbieta; Hałabiś, Magdalena; Baranowicz-Gąszczyk, Iwona; Solski, Janusz; Książek, Andrzej

    2011-05-01

    Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles

  16. Using of AFLP to evaluate gamma-irradiated amaranth mutants

    Directory of Open Access Journals (Sweden)

    Labajová Mária

    2013-01-01

    Full Text Available To determine which of several gamma-irradiated mutants of amaranth Ficha cultivar and K-433 hybrid are most genetically similar to their non-irradiated control genotypes, we performed amplified fragment length polymorphism (AFLP based analysis. A total of 40 selective primer combinations were used in reported analyses. First analyses of gamma-irradiated amaranth mutant lines were done used the AFLP. In the study, primers with the differentiation ability for all analysed mutant lines are reported. The very specific changes in the mutant lines´ non-coding regions based on AFLP length polymorphism were analysed. Mutant lines of the Ficha cultivar (C15, C26, C27, C82, C236 shared a genetic dissimilarity of 0,11 and their ISSR profiles are more similar to the Ficha than those of K-433 hybrid mutant lines. The K-433 mutant lines (D54, D279, D282 shared genetic dissimilarity of 0,534 but are more distinct to their control plant as a whole, as those of the Ficha mutant lines. Different AFLP fingerprints patters of the mutant lines when compared to the Ficha cultivar and K-433 hybrid AFLP profiles may be a consequence of the complex response of the intergenic space of mutant lines to the gamma-radiance. Although a genetic polymorphism was detected within accessions, the AFLP markers successfully identified all the accessions. The AFLP results are discussed by a combination of biochemical characteristics of mutant lines and their control genotypes.

  17. Distribution of soluble amino acids in maize endosperm mutants

    Directory of Open Access Journals (Sweden)

    Toro Alejandro Alberto

    2003-01-01

    Full Text Available For human nutrition the main source of vegetable proteins are cereal and legume seeds. The content of total soluble amino acids in mature endosperm of wild-type, opaque and floury maize (Zea mays L. mutants were determined by HPLC. The total absolute concentration of soluble amino acids among the mutants varied depending on the mutant. The o11 and o13 mutants exhibited the highest average content, whereas o10, fl3 and fl1 exhibited the lowest average content. In general, the mutants exhibited similar concentrations of total soluble amino acids when compared to the wild-type lines, with the clear exception of mutants o11 and fl1, with the o11 mutant exhibiting a higher concentration of total soluble amino acids when compared to its wild-type counterpart W22 and the fl1 mutant a lower concentration when compared to its wild-type counterpart Oh43. For methionine, the mutants o2 and o11 and wild-type Oh43 exhibited the highest concentrations of this amino acid. Significant differences were not observed between mutants for other amino acids such as lysine and threonine. The high lysine concentrations obtained originally for these mutants may be due to the amino acids incorporated into storage proteins, but not those present in the soluble form.

  18. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    NARCIS (Netherlands)

    Beulens, J.W.J.; Berg, van den R.; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results Eleven lean (BMI: 18.5¿25 kg/m2) and 9 overweight (BMI &g

  19. Changes in the triglyceride-rich lipoproteins and the response to dietary cholesterol in man.

    NARCIS (Netherlands)

    Demacker, P.N.M.; Glatz, J.F.C.; Katan, M.B.

    1988-01-01

    The effect of a cholesterol-enriched diet was studied in nine healthy volunteers with special emphasis to the changes which occurred in the triglyceride-rich lipoproteins (d<1.019 g/ml). Compared to the habitual diet, a moderately increased intake of cholesterol (from 300–900 mg/day) resulted in cha

  20. Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the low density lipoprotein receptor

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov;

    2005-01-01

    Mutations in apolipoprotein B (APOB) may reduce binding of low density lipoprotein (LDL) to the LDL receptor and cause hypercholesterolemia. We showed that heterozygotes for a new mutation in APOB have hypobetalipoproteinemia, despite a reduced binding of LDL to the LDL receptor. APOB R3480P hete...

  1. Lipid, lipoprotein, and apolipoprotein profiles in active and sedentary men with tetraplegia

    NARCIS (Netherlands)

    Dallmeijer, A J; Hopman, M T; van der Woude, L H

    1997-01-01

    OBJECTIVE: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. DESIGN: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13 seden

  2. Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a).

    NARCIS (Netherlands)

    Urgert, R.; Weusten-van der Wouw, M.P.M.E.; Hovenier, R.; Lund-Larsen, P.G.; Katan, M.B.

    1996-01-01

    OBJECTIVES: Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boile

  3. High-density lipoproteins and coronary artery disease: a single-center cohort study

    NARCIS (Netherlands)

    Schaffer, A.; Verdoia, M.; Barbieri, L.; Aprami, T.M.; Suryapranata, H.; Marino, P.; Luca, G.D.

    2014-01-01

    Our goal was to estimate the role of high-density lipoprotein cholesterol (HDL-C) in predicting the prevalence and extent of coronary artery disease (CAD) in 3280 patients undergoing coronary angiography. Predictors of lower HDL levels (<32 mg/dL) were male gender (P < .001), diabetes mellitus

  4. 21 CFR 866.5600 - Low-density lipoprotein immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system. 866.5600 Section 866.5600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young...

  5. Impact of lipids and lipoproteins on hepatitis C virus infection and virus neutralization.

    Science.gov (United States)

    Vercauteren, Koen; Mesalam, Ahmed Atef; Leroux-Roels, Geert; Meuleman, Philip

    2014-11-21

    Hepatitis C virus (HCV) infections represent a major global health problem. End-stage liver disease caused by chronic HCV infection is a major indication for liver transplantation. However, after transplantation the engrafted liver inevitably becomes infected by the circulating virus. Direct acting antivirals are not yet approved for use in liver transplant patients, and limited efficacy and severe side effects hamper the use of pegylated interferon combined with ribavirin in a post-transplant setting. Therefore, alternative therapeutic options need to be explored. Viral entry represents an attractive target for such therapeutic intervention. Understanding the mechanisms of viral entry is essential to define the viral and cellular factors involved. The HCV life cycle is dependent of and associated with lipoprotein physiology and the presence of lipoproteins has been correlated with altered antiviral efficacy of entry inhibitors. In this review, we summarise the current knowledge on how lipoprotein physiology influences the HCV life cycle. We focus especially on the influence of lipoproteins on antibodies that target HCV envelope proteins or antibodies that target the cellular receptors of the virus. This information can be particularly relevant for the prevention of HCV re-infection after liver transplantation.

  6. Method-dependent increase in lipoprotein(a) in insulin-dependent diabetes mellitus during pregnancy

    NARCIS (Netherlands)

    Pekelharing, HLM; Aalders, NL; Visser, GHA; vanDoormaal, JJ; Kleinveld, HA; vanRijn, HJM; Bouma, Bonno N.

    1995-01-01

    The current prevalent view is that plasma lipoprotein(a) [Lp(a)] concentrations are under strong genetic control. Most dietary and drug interventions seem to have little or no effect on plasma Lp(a) levels. However, evidence for a possible regulatory role of hormones is accumulating, for instance, f

  7. Lipoprotein-associated phospholipase A2 and coronary calcification - The Rotterdam coronary calcification study

    NARCIS (Netherlands)

    Kardys, Isabella; Oei, Hok-Hay S.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jacqueline C. M.

    2007-01-01

    Objectives: Although several studies have recently suggested that lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent predictor of coronary events, only one study has examined the association between Lp-PLA2 and coronary calcification, using young adults. We investigated the associat

  8. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Feitosa, Mary F; Wojczynski, Mary K; Straka, Robert

    2014-01-01

    The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights...

  9. Association of lipoprotein levels with mortality in subjects aged 50 + without previous diabetes or cardiovascular disease

    DEFF Research Database (Denmark)

    Bathum, Lise; Depont Christensen, René; Engers Pedersen, Lars

    2013-01-01

    This study aimed to investigate the association of lipoprotein and triglyceride levels with all-cause mortality in a population free from diabetes and cardiovascular disease (CVD) at baseline. The European Guidelines on cardiovascular disease prevention state that in general total cholesterol (TC...

  10. The HDL hypothesis : does high-density lipoprotein protect from atherosclerosis?

    NARCIS (Netherlands)

    Vergeer, Menno; Holleboom, Adriaan G; Kastelein, John J P; Kuivenhoven, Jan Albert

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  11. Cigarette smoking and its association with serum lipid/lipoprotein among Chinese nonagenarians/centenarians

    Directory of Open Access Journals (Sweden)

    Yan-Ling Zhang

    2012-07-01

    Full Text Available Abstract Objective Cigarette smoking had been confirmed as an increased risk for dyslipidemia, but none of the evidence was from long-lived population. In present study, we detected relationship between cigarette smoking habits and serum lipid/lipoprotein (serum Triglyceride (TG, Total cholesterol (TC, Low-density lipoprotein (LDL and high-density lipoprotein (HDL among Chinese Nonagenarians/Centenarian. Methods The present study analyzed data from the survey that was conducted on all residents aged 90 years or more in a district, there were 2,311,709 inhabitants in 2005. Unpaired Student’s t test, χ2 test, and multiple logistic regression were used to analyze datas. Results The individuals included in the statistical analysis were 216 men and 445 women. Current smokers had lower level of TC (4.05 ± 0.81 vs. 4.21 ± 0.87, t = 2.403, P = 0.017 and lower prevalence of hypercholesteremia (9.62% vs. 15.13%, χ2 = 3.018,P = 0.049 than nonsmokers. Unadjusted and adjusted multiple logistic regressions showed that cigarette smoking was not associated with risk for abnormal serum lipid/lipoprotein. Conclusions In summary, we found that among Chinese nonagenarians/centenarians, cigarette smoking habits were not associated with increased risk for dyslipidemia, which was different from the association of smoking habits with dyslipidemia in general population.

  12. Gold Nanoparticles Enhanced Microchip Capillary Electrophoresis for Detection of Serum Lipoprotein

    Institute of Scientific and Technical Information of China (English)

    WANG Hua; WANG DaXin; CAO Li; CHEN Xia

    2009-01-01

    @@ We describe here the use of gold nanoparticles (AuNPs) in conjunction with chip-based capillary electrophoresis (CE) to improve the selectivity between lipoprotein fractions and increase the efficiency of the separation.AuNPs were added into the running buffer to manipulate solution and control the electroosmotic flow (EOF).

  13. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Benn, Marianne; Tybjaerg-Hansen, Anne

    2008-01-01

    of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates....

  14. Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-monoacylglycerol in mice

    DEFF Research Database (Denmark)

    Kleberg, Karen; Nielsen, Louise Lundeman; Stuhr-Hansen, Nicolai;

    2014-01-01

    2-Monoacylglycerols are gaining increasing interest as signaling lipids, beyond endocannabinoids, for example, as ligands for the receptor GPR119 and as mediators of insulin secretion. In the vascular system, they are formed by the action of lipoprotein lipase (LPL); however, their further dispos...

  15. Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure

    Directory of Open Access Journals (Sweden)

    Brian J. Bahnson

    2010-03-01

    Full Text Available Plasma platelet-activating factor acetylhydrolase (PAF-AH, also called lipoprotein-associated phospholipase A2 (Lp-PLA2, is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.

  16. Effect of a Marathon Run on Serum Lipoproteins, Creatine Kinase, and Lactate Dehydrogenase in Recreational Runners

    Science.gov (United States)

    Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A.

    2005-01-01

    The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride…

  17. High-density lipoproteins: a novel therapeutic target for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    TS Mohamed Saleem

    2011-01-01

    Full Text Available TS Mohamed Saleem1, PV Sandhya Rani1, K Gauthaman21Department of Pharmacology, Annamacharya College of Pharmacy, New Boyanapalli, Andhrapradesh, India; 2Department of Drug Technology, Faculty of Medical Technology, Derna, LibyaAbstract: Cardiovascular disease has a high rate of mortality in both Western and developing countries. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for cardiovascular disease. Atherothrombosis with low levels of high-density lipoprotein (HDL and high levels of low-density lipoprotein is a major risk factor for atherosclerosis-induced cardiovascular disease. Lipid-lowering drugs like statins, niacin, fibrates, and some newer agents, ie, the apolipoprotein A-I mimetics and the cholesteryl ester transfer protein inhibitors, not only increase HDL levels but are also effective in reducing key atherogenic lipid components, including triglyceride-rich lipoproteins. The aim of this review is to discuss the accumulating evidence suggesting that HDL possesses a diverse range of biological actions, and that increasing HDL levels by drug treatment may be beneficial in the prevention of cardiovascular disease.Keywords: cardiovascular disease, lipoproteins, statins, apolipoprotein, atherosclerosis

  18. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin Levels in Type 2 Diabetes Mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) have been associated with a decreased risk of these complications. The aim in this st...

  19. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  20. Familial lipoprotein lipase-activity deficiency: study of total body fatness and subcutaneous fat tissue distribution.

    Science.gov (United States)

    Brun, L D; Gagné, C; Julien, P; Tremblay, A; Moorjani, S; Bouchard, C; Lupien, P J

    1989-10-01

    Total body fatness and subcutaneous fat tissue distribution were evaluated in 19 hyperchylomicronemic patients. Eleven were males, aged 10 to 57 years, and eight were females, aged 13 to 46 years. Familial lipoprotein-lipase-activity deficiency was diagnosed by the absence of lipoprotein-lipase activity in the plasma withdrawn ten and 20 minutes after intravenous injection of ten units of heparin per kilogram of body weight. The 19 patients had skin-fold measurements for evaluation of subcutaneous fat distribution. Fifteen also underwent body density measurements by underwater weighing. Percent body fat was calculated from body density. These anthropometric data were plotted against the regression curves of 1638 normal controls of both sexes (aged 10 to 54 years) for fat tissue weight, percent body fat, subcutaneous fat/total fat mass ratio and trunk/extremity skin-fold ratio. Impairments in the process of building fat tissue reserves could not be shown in the 19 hyperchylomicronemic patients, in spite of the absence of lipoprotein-lipase activity in their postheparin plasma. It is hypothesized that normal fat tissue mass in these patients could be due partly to de novo synthesis of fatty acids by adipocytes, hydrolysis of plasma triglycerides by hepatic lipase, and/or contribution of a specific fat-tissue lipase to the catabolism of plasma triglyceride-rich lipoproteins.

  1. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Rashid Nazir [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Kok, Wim Th., E-mail: W.Th.Kok@uva.nl [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Schoenmakers, Peter J. [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands)

    2009-11-03

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples.

  2. The relationship between lipoprotein lipase-447C/G genepolymorphism and cerebral infarction in the elderly

    Institute of Scientific and Technical Information of China (English)

    胡晓雁

    2013-01-01

    Objective To explore the relationship between the lipoprotein lipase(LPL)-447C/G gene polymorphism and cerebral infarction in the elderly. Methods This was a case-control study,which enrolled 206 cases with cerebral infarction in the elderly and 203 elderly

  3. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVES: The purpose of this study was to determine whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism) prospectively associate with increased risk of aortic valve stenosis (AVS). BACKGROUND: The etiologic...

  4. Comparison of Total Antioxidant Capacity Oxidative Stress and Blood Lipoprotein Parameters in Volleyball Players and Sedentary

    Science.gov (United States)

    Gokhan, Ismail

    2013-01-01

    This study aims to measure, then compare sedentary blood lipoproteins, oxidant- antioxidant state and oxidative stress index in volleyball players. The experimental group of the research consists of regularly practising 20 boys between the ages of 12 and 17, and the control group comprises 32 children practising no particular sports branch, 12 of…

  5. Palmitic acid and linoleic acid metabolism in Caco-2 cells: Different triglyceride synthesis and lipoprotein secretion

    NARCIS (Netherlands)

    van Greevenbroek, M.M.J.; Voorhout, W.F.; Erkelens, D.W.; van Meer, G.; de Bruin, T.W.A.

    1995-01-01

    Polarized monolayers of intestinal Caco-2 cells were used to study the effects of saturated palmitic acid (16:0) and polyunsaturated linoleic acid (18:2) on triglyceride synthesis and lipoprotein secretion. Monolayers were incubated for 24 h, at the apical or lumenal side, with palmitic acid (16:0)

  6. Low-density lipoprotein-lowering strategies: target versus maximalist versus population percentile.

    NARCIS (Netherlands)

    Sniderman, A.D.; Graaf, J. de; Couture, P.

    2012-01-01

    PURPOSE OF REVIEW: Maximalist low-density lipoprotein (LDL)-lowering strategies such as lowering LDL as much as possible or, alternatively, using the most potent LDL-lowering regimens have become increasingly popular. Almost all attention has focused on the potential advantages of these approaches w

  7. Low density lipoprotein : structure, dynamics, and interactions of apoB-100 with lipids

    NARCIS (Netherlands)

    Murtola, Teemu; Vuorela, Timo A.; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL's st

  8. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne;

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...

  9. Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans

    Science.gov (United States)

    Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not ...

  10. Effect of dietary cis and trans fatty acids on serum lipoprotein(a) levels in humans.

    NARCIS (Netherlands)

    Mensink, R.P.; Zock, P.L.; Katan, M.B.; Hornstra, G.

    1992-01-01

    Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a contr

  11. Lipoprotein glomerulopathy: a case report of a rare disease in a brazilian child

    Directory of Open Access Journals (Sweden)

    Karla Lais Pegas

    2014-03-01

    Full Text Available Lipoprotein glomerulopathy (LPG is a rare autosomal recessive glomerulopathy associated with the deposition of lipoprotein thrombi in the capillary lumina due to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase in serum apoliprotein E (apoE are characteristic clinical data. The compromised patients can present nephrotic syndrome, hematuria, and progressive renal failure. Herein, the authors present the first described case of LPG in a Brazilian male patient, 11 years, who presented with a steroid-resistant nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly enlarged glomerulus, with dilated capillary loops and weak eosinophilic lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and veins showed normal histologic aspect. Genotypic study for the apoE gene showed the presence of the alleles E3 and E4. The diagnosis of LPG was then performed. The patient received lipid-lowering treatment. After 2 years of follow-up, renal function is gradually decreasing, with persisting heavy proteinuria, despite a marked decrease in serum cholesterol and triglycerides levels.

  12. Lipophilic antioxidants and polyunsaturated fatty acids in lipoprotein classes: distribution and interaction

    DEFF Research Database (Denmark)

    Sunesen, V.H.; Weber, Christine; Hølmer, Gunhild Kofoed

    2001-01-01

    Objective: To study the lipoprotein distribution of supplemented coenzyme Q(10) (CoQ(10)), vitamin E, and polyunsaturated fatty acids (PUFA). Design: Balanced three- period crossover study. Setting: University research unit. Subjects: Eighteen apparently healthy free-living non-smoking volunteers...

  13. Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

    2014-01-01

    Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

  14. Ganglioside embedded in reconstituted lipoprotein binds cholera toxin with elevated affinity.

    Science.gov (United States)

    Bricarello, Daniel A; Mills, Emily J; Petrlova, Jitka; Voss, John C; Parikh, Atul N

    2010-09-01

    The ability to exogenously present cell-surface receptors in high-affinity conformations in a synthetic system offers an opportunity to provide host cells with protection from pathogenic toxins. This strategy requires improvement of the synthetic receptor binding affinity against its native counterpart, particularly with polyvalent toxins where clustering of membrane receptors can hinder binding. Here we demonstrate that reconstituted lipoprotein, nanometer-sized discoidal lipid bilayers bounded by apolipoprotein and functionalized by incorporation of pathogen receptors, provides a means to enhance toxin-receptor binding through molecular-level control over the receptor microenvironment (specifically, its rigidity, composition, and heterogeneity). Using a Foerster Resonance Energy Transfer (FRET)-based assay, we found that reconstituted lipoprotein incorporating low concentrations of ganglioside monosialotetrahexosylganglioside (GM1) binds polymeric cholera toxin with significantly higher affinity than liposomes or supported lipid bilayers, most likely a result of the enhanced control over receptor clustering provided by the lipoprotein platform. Using wide-area epifluorescence, we found that this enhanced binding capacity can be effectively utilized to divert cholera toxin away from populations of healthy mammalian cells. In summary, we found that reconstitutions of high-density lipoprotein can be engineered to include specific pathogen receptors; that their pathogen binding affinity is altered, presumably due to attenuation of receptor aggregation; and that these assemblies are effective at protecting cells from biological toxins.

  15. Active lipoprotein precursors in the gram-positive eubacterium Lactococcus lactis

    NARCIS (Netherlands)

    Venema, R; Tjalsma, H; van Dijl, J.M; Leenhouts, K.; Buist, G; Venema, G

    2003-01-01

    Lipid-modified proteins play important roles at the interface between eubacterial cells and their environment. The importance of lipoprotein processing by signal peptidase II (SPase II) is underscored by the fact that this enzyme is essential for viability of the Gram-negative eubacterium Escherichi

  16. High-Density Lipoprotein Modulates Glucose Metabolism in Patients With Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Drew, Brian G.; Duffy, Stephen J.; Formosa, Melissa F.; Natoli, Alaina K.; Henstridge, Darren C.; Penfold, Sally A.; Thomas, Walter G.; Mukhamedova, Nigora; de Courten, Barbora; Forbes, Josephine M.; Yap, Felicia Y.; Kaye, David M.; van Hall, Gerrit; Febbraio, Mark A.; Kemp, Bruce E.; Sviridov, Dmitri; Steinberg, Gregory R.; Kingwell, Bronwyn A.

    2009-01-01

    Background-Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activat

  17. Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

    NARCIS (Netherlands)

    Beulens, J.W.J.; Berg, R. van den; Kok, F.J.; Helander, A.; Vermunt, S.H.F.; Hendriks, H.F.J.

    2008-01-01

    Background and aims: To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results: Eleven lean (BMI: 18.5-25 kg/m2) and 9 overweight (BMI

  18. Increased Antioxidant Quality Versus Lower Quantity Of High Density Lipoprotein In Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Aydin Ozgur

    2015-10-01

    Full Text Available Background: Oxidative stress may be involved in the pathogenesis of every human disease. To understand its possible role in benign prostatic hyperplasia (BPH, we measured the overall oxidative status of patients with BPH and the serum activity of the high density lipoprotein (HDL-related antioxidant enzymes paraoxonase 1 (PON1 and arylesterase (ARE.

  19. Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

    NARCIS (Netherlands)

    Schalkwijk, C.G.; Vermeer, M.A.; Stehouwer, C.D.A.; Koppele, J. te; Princen, H.M.G.; Hinsbergh, V.W.M. van

    1998-01-01

    In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diab

  20. How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

    DEFF Research Database (Denmark)

    Karilainen, Topi; Vuorela, Timo; Vattulainen, Ilpo

    2015-01-01

    We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect...

  1. Lipoprotein subfractions in metabolic syndrome and obesity: clinical significance and therapeutic approaches.

    Science.gov (United States)

    Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R; Mikhailidis, Dimitri P; Rizzo, Manfredi

    2013-03-18

    Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk.

  2. Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Manfredi Rizzo

    2013-03-01

    Full Text Available Small, dense low density lipoprotein (sdLDL represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG, very low density lipoprotein (VLDL and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk.

  3. High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans

    NARCIS (Netherlands)

    Birjmohun, Rakesh S; van Leuven, Sander I; Levels, Johannes H M; van 't Veer, Cornelis; Kuivenhoven, Jan Albert; Meijers, Joost C M; Levi, Marcel; Kastelein, John J P; van der Poll, Tom; Stroes, Erik S G

    2007-01-01

    OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in huma

  4. Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

    NARCIS (Netherlands)

    Hendriks, H.F.J.; Veenstra, J.; Tol, A. van; Groener, J.E.M.; Schaafsma, G.

    1998-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels we

  5. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...... and type of mutation (LDL receptor [LDLR] or APOB R3500Q) for cholesterol phenotype....

  6. Characterization of Lipoprotein Composition and Function in Pediatric Psoriasis Reveals a More Atherogenic Profile.

    Science.gov (United States)

    Tom, Wynnis L; Playford, Martin P; Admani, Shehla; Natarajan, Balaji; Joshi, Aditya A; Eichenfield, Lawrence F; Mehta, Nehal N

    2016-01-01

    Psoriasis is associated with increased cardiovascular disease in adults, but the risk profile of children with psoriasis remains to be fully characterized. We measured lipoprotein composition and function in 44 patients with pediatric psoriasis and 44 age- and sex-matched healthy controls, using nuclear magnetic resonance spectroscopy and a validated ex vivo assay of high-density lipoprotein cholesterol efflux capacity. The mean age of the patients was 13 years and the population was ethnically diverse. Children with psoriasis had higher waist-to-hip ratios (0.85 vs. 0.80; P psoriasis was associated with higher apolipoprotein B concentrations (72.4 vs. 64.6; P = 0.02), decreased large high-density lipoprotein particles (5.3 vs. 6.7; P psoriasis have a more atherogenic cardiometabolic risk profile, with evidence of insulin resistance and lipoprotein dysfunction by particle size, number, and functional assessment. These findings may provide a basis for the observed link later in life between psoriasis and cardiovascular disease, and support the need to screen and educate young patients to minimize later complications.

  7. Effects of plant sterols and olive oil phenols on serum lipoproteins in humans

    NARCIS (Netherlands)

    Vissers, M.N.

    2001-01-01

    The studies described in this thesis investigated whether minor components from vegetable oils can improve health by decreasing cholesterol concentrations or oxidative modification of low-density-lipoprotein (LDL) particles.The plant sterolsβ-sitosterol and sitostanol are known to decrease cholester

  8. Association of low density lipoprotein levels and glycaemic control in type-2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yathish TR.

    2010-01-01

    Full Text Available Earlier diabetes mellitus (DM was thought to be a disease of carbohydrate metabolism. Looking at the effects of insulin deficiency on carbohydrate and lipid metabolism, diabetes mellitus is now being called more a disease of lipid metabolism than carbohydrate metabolism. A cross-sectional study was conducted during March 2005 to March 2006 to study the low-density lipoproteins (LDL levels in diabetes mellitus and its relation to glycaemic control. LDL levels were estimated. Comparison of lipid levels were made between group of diabetic patients with glycated hemoglobin less than 8.0% and a group of diabetic patients with glycated hemoglobin more than 8.0% and the controls. The lipid fractions i.e. total cholesterol (TC, triglycerides (TG, and low-density lipoprotein (LDL levels were higher in the poorly controlled diabetes patients as compared to well controlled diabetic patients and nondiabetic patients. Increased levels of low-density lipoprotein may be a contributory factor to the high risk of atherosclerosis induced coronary artery disease observed in diabetes mellitus patients. Reduction of blood glucose levels is likely to reduce low density lipoprotein levels and the risk of complication, with the lowest risk being in those with glycosylated hemoglobin values in the normal range ie. Less than 8.0%

  9. [Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].

    Science.gov (United States)

    Sokolov, E I; Metel'skaia, V A; Perova, N V; Shchukina, G N

    2006-01-01

    The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.

  10. Apolipoprotein A5 and lipoprotein lipase interact to modulate anthropometric measures in Hispanics of Caribbean origin

    Science.gov (United States)

    Apolipoprotein A5 (APOA5) and lipoprotein lipase (LPL) proteins interact functionally to regulate lipid metabolism, and single nucleotide polymorphisms (SNPs) for each gene have also been associated independently with obesity risk. Evaluating gene combinations may be more effective than single SNP a...

  11. Mechanism underlying the inner membrane retention of Escherichia coli lipoproteins caused by Lol avoidance signals.

    Science.gov (United States)

    Hara, Takashi; Matsuyama, Shin-ichi; Tokuda, Hajime

    2003-10-10

    Escherichia coli lipoproteins are localized to either the inner or outer membrane depending on the residue at position 2. The inner membrane retention signal, Asp at position 2 in combination with certain residues at position 3, functions as a Lol avoidance signal, i.e. the signal inhibits the recognition of lipoproteins by LolCDE that releases lipoproteins from the inner membrane. To understand the role of the residue at position 2, outer membrane-specific lipoproteins with Cys at position 2 were subjected to chemical modification followed by the release reaction in reconstituted proteoliposomes. Sulfhydryl-specific introduction of nonprotein molecules or a negative charge to Cys did not inhibit the LolCDE-dependent release. In contrast, oxidation of Cys to cysteic acid resulted in generation of the Lol avoidance signal, indicating that the Lol avoidance signal requires a critical length of negative charge at the second residue. Furthermore, not only modification of the carboxylic acid of Asp at position 2 but also that of the amine of phosphatidylethanolamine abolished the Lol avoidance function. Based on these results, the Lol avoidance mechanism is discussed.

  12. Induction of oxygen free radical generation in human monocytes by lipoprotein(a)

    DEFF Research Database (Denmark)

    Riis Hansen, P; Kharazmi, A; Jauhiainen, M

    1994-01-01

    The mechanism behind the association of elevated plasma lipoprotein(a) [Lp(a)] levels with atherosclerotic disease is unknown. In the present study, Lp(a) induced generation of oxygen free radicals by monocytes from selected healthy individuals in vitro. This observation may provide a link between...

  13. Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Callow, M.J.; Stoltzfus, L.J.; Rubin, E.M. [Lawrence Berkeley Lab., CA (United States); Lawn, R.M. [Stanford Univ., CA (United States)

    1994-03-15

    The atherogenic macromolecule lipoprotein(a) [Lp(a)] has resisted in vivo analyses partly because it is found in a limited number of experimental animals. Although transgenic mice expressing human apolipoprotein (a) [apo(a)] have previously been described, they failed to assemble Lp(a) particles because of the inability of human apo(a) to associate with mouse apolipoprotein B (apoB). The authors isolated a 90-kilobase P1 phagemid containing the human apoB gene and with this DNA generated 13 lines of transgenic mice of which 11 expressed human apoB. The human apoB transcript was expressed and edited in the liver of the transgenic mice. Plasma concentrations of human apoB, as well as low density lipoprotein (LDL), were related to transgene copy number; the transgenic line with the most copies of human apoB had a >4-fold increase in LDL cholesterol compared with nontransgenics and a lipoprotein profile similar to that of humans. When human apoB and apo(a) transgenic mice were bred together, plasma apo(a) in mice expressing both human proteins was tightly associated with lipoproteins in the LDL density region. These studies demonstrate the successful expression of human apoB and the efficient assembly of Lp(a) in mice.

  14. Variability in lipoprotein concentrations in serum after prolonged storage at -20°C.

    NARCIS (Netherlands)

    Tiedink, H.G.M.; Katan, M.B.

    1989-01-01

    The effects of freezing and storage at − 20° C of serum on the measurement of cholesterol and triglycerides concentrations in lipoprotein fractions separated by density gradient ultracentrifugation were investigated. Fresh, fasting, normolipidemic sera from 24 healthy individuals were divided into a

  15. Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

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    Márcia Dias Teixeira Carvalho

    2014-01-01

    Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

  16. The P2Y2 receptor mediates uptake of matrix-retained and aggregated low density lipoprotein in primary vascular smooth muscle cells

    Science.gov (United States)

    Dissmore, Tixieanna; Seye, Cheikh I.; Medeiros, Denis M.; Weisman, Gary A.; Bardford, Barry; Mamedova, Laman

    2016-01-01

    Background and aims The internalization of aggregated low-density lipoproteins (agLDL) mediated by low-density lipoprotein receptor related protein (LRP1) may involve the actin cytoskeleton in ways that differ from the endocytosis of soluble LDL by the LDL receptor (LDLR). This study aims to define novel mechanisms of agLDL uptake through modulation of the actin cytoskeleton, to identify molecular targets involved in foam cell formation in vascular smooth muscle cells (VSMCs). The critical observation that formed the basis for these studies is that under pathophysiological conditions, nucleotide release from blood-derived and vascular cells activates SMC P2Y2 receptors (P2Y2Rs) leading to rearrangement of the actin cytoskeleton and cell motility. Therefore, we tested the hypothesis that P2Y2R activation mediates agLDL uptake by VSMCs. Methods Primary VSMCs were isolated from aortas of wild type (WT) C57BL/6 and.P2Y2R−/− mice to investigate whether P2Y2R activation modulates LRP1 expression. Cells were transiently transfected with cDNA encoding a hemagglutinin-tagged (HA-tagged) WT P2Y2R, or a mutant P2Y2R that unlike the WT P2Y2R does not bind the cytoskeletal actin-binding protein filamin-A (FLN-A). Results P2Y2R activation significantly increased agLDL uptake, and LRP1 mRNA expression decreased in P2Y2R−/− VSMCs versus WT. SMCs, expressing P2Y2R defective in FLN-A binding, exhibit 3-fold lower LDLR expression levels than SMCs expressing WT P2Y2R, while cells transfected with WT P2Y2R show greater agLDL uptake in both WT and P2Y2R−/− VSMCs versus cells transfected with the mutant P2Y2R. Conclusions Together, these results show that both LRP1 and LDLR expression and agLDL uptake are regulated by P2Y2R in VSMCs, and that agLDL uptake due to P2Y2R activation is dependent upon cytoskeletal reorganization mediated by P2Y2R binding to FLN-A. PMID:27522265

  17. High density lipoprotein as a source of cholesterol for adrenal steroidogenesis : A study in individuals with low plasma HDL-C

    NARCIS (Netherlands)

    Bochem, Andrea E.; Holleboom, Adriaan G.; Romijn, Johannes A.; Hoekstra, Menno; Dallinga-Thie, Geesje M.; Motazacker, Mahdi M.; Hovingh, G. Kees; Kuivenhoven, Jan A.; Stroes, Erik S. G.

    2013-01-01

    Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To st

  18. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

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    Miloslava Hodúlová

    Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

  19. A Pressure-dependent Model for the Regulation of Lipoprotein Lipase by Apolipoprotein C-II*

    Science.gov (United States)

    Meyers, Nathan L.; Larsson, Mikael; Olivecrona, Gunilla; Small, Donald M.

    2015-01-01

    Apolipoprotein C-II (apoC-II) is the co-factor for lipoprotein lipase (LPL) at the surface of triacylglycerol-rich lipoproteins. LPL hydrolyzes triacylglycerol, which increases local surface pressure as surface area decreases and amphipathic products transiently accumulate at the lipoprotein surface. To understand how apoC-II adapts to these pressure changes, we characterized the behavior of apoC-II at multiple lipid/water interfaces. ApoC-II adsorption to a triacylglycerol/water interface resulted in large increases in surface pressure. ApoC-II was exchangeable at this interface and desorbed on interfacial compressions. These compressions increase surface pressure and mimic the action of LPL. Analysis of gradual compressions showed that apoC-II undergoes a two-step desorption, which indicates that lipid-bound apoC-II can exhibit at least two conformations. We characterized apoC-II at phospholipid/triacylglycerol/water interfaces, which more closely mimic lipoprotein surfaces. ApoC-II had a large exclusion pressure, similar to that of apoC-I and apoC-III. However, apoC-II desorbed at retention pressures higher than those seen with the other apoCs. This suggests that it is unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from the lipoprotein surface. Upon rapid compressions and re-expansions, re-adsorption of apoC-II increased pressure by lower amounts than its initial adsorption. This indicates that apoC-II removed phospholipid from the interface upon desorption. These results suggest that apoC-II regulates the activity of LPL in a pressure-dependent manner. ApoC-II is provided as a component of triacylglycerol-rich lipoproteins and is the co-factor for LPL as pressure increases. Above its retention pressure, apoC-II desorbs and removes phospholipid. This triggers release of LPL from lipoproteins. PMID:26026161

  20. Indy mutants: live long and prosper

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    Stewart eFrankel

    2012-02-01

    Full Text Available Indy encodes the fly homologue of a mammalian transporter of di and tricarboxylatecomponents of the Krebs cycle. Reduced expression of fly Indy or two of the C. elegansIndy homologs leads to an increase in life span. Fly and worm tissues that play key roles inintermediary metabolism are also the places where Indy genes are expressed. One of themouse homologs of Indy (mIndy is mainly expressed in the liver. It has been hypothesizedthat decreased INDY activity creates a state similar to caloric restriction (CR. Thishypothesis is supported by the physiological similarities between Indy mutant flies on highcalorie food and control flies on CR, such as increased physical activity and decreases inweight, egg production, triglyceride levels, starvation resistance, and insulin signaling. Inaddition, Indy mutant flies undergo changes in mitochondrial biogenesis also observed inCR animals. Recent findings with mIndy knockout mice support and extend the findingsfrom flies. mIndy-/- mice display an increase in hepatic mitochondrial biogenesis, lipidoxidation and decreased hepatic lipogenesis. When mIndy-/- mice are fed high calorie foodthey are protected from adiposity and insulin resistance. These findings point to INDY as apotential drug target for the treatment of metabolic syndrome, type 2 diabetes and obesity.

  1. Auxin physiology of the tomato mutant diageotropica

    Science.gov (United States)

    Daniel, S. G.; Rayle, D. L.; Cleland, R. E.

    1989-01-01

    The tomato (Lycopersicon esculentum, Mill.) mutant diageotropica (dgt) exhibits biochemical, physiological, and morphological abnormalities that suggest the mutation may have affected a primary site of auxin perception or action. We have compared two aspects of the auxin physiology of dgt and wild-type (VFN8) seedlings: auxin transport and cellular growth parameters. The rates of basipetal indole-3-acetic acid (IAA) polar transport are identical in hypocotyl sections of the two genotypes, but dgt sections have a slightly greater capacity for IAA transport. 2,3,5-Triiodobenzoic acid and ethylene reduce transport in both mutant and wild-type sections. The kinetics of auxin uptake into VFN8 and dgt sections are nearly identical. These results make it unlikely that an altered IAA efflux carrier or IAA uptake symport are responsible for the pleiotropic effects resulting from the dgt mutation. The lack of auxin-induced cell elongation in dgt plants is not due to insufficient turgor, as the osmotic potential of dgt cell sap is less (more negative) than that of VFN8. An auxin-induced increase in wall extensibility, as measured by the Instron technique, only occurs in the VFN8 plants. These data suggest dgt hypocotyls suffer a defect in the sequence of events culminating in auxin-induced cell wall loosening.

  2. Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

    Science.gov (United States)

    Srivastava, Anand; Adams-Huet, Beverley; Vega, Gloria L; Toto, Robert D

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, p<0.01), V+I C(−18.8% vs +21.3%, p<0.01), and V+I-ApoB (−13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. Trial registration number NCT00381134; Results. PMID:27388615

  3. Lipoprotein composition and serum cholesterol ester fatty acids in nonwesternized Melanesians.

    Science.gov (United States)

    Lindeberg, S; Nilsson-Ehle, P; Vessby, B

    1996-02-01

    In this study, the relationships between dietary fat [as measured by serum cholesterol ester fatty acids (CE-FA)], age, smoking, body mass index, and serum lipids were analyzed in 151 subsistence horticulturalists, aged 20-86 yr, from Kitava, Trobriand Islands, Papua New Guinea. Their diet consists of tubers, fruit, coconut, fish, and vegetables with a negligible influence of western food and alcohol. Total fat intake is low [21% of energy (en%)], while saturated fat intake from coconuts is high (17 en%, mainly lauric and myristic acid). In multivariate analysis, 11-43% of the variation of the serum lipoprotein composition was explained by CE-FA, age, and smoking habits. The proportion of CE20:5n-3 explained much of the variation of triglycerides (TG, negative relation) and high density lipoprotein-cholesterol (HDL-C, positive) in both sexes and serum apolipoprotein A1 (ApoA1, positive) in the males. CE16:0 was positively related to TG and negatively related to HDL-C and ApoA1 in both sexes, and in males it related negatively to total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). In males, negative relationships were present between CE18:2n-6 and TC and between CE14:0 and serum lipoprotein(a). Smoking was independently associated with lower ApoA1 in both sexes and with lower HDL-C and higher TG, TC, LDL-C, and apolipoprotein B in males. In conclusion, marine n-3 fatty acids and linoleic acid showed the same potentially beneficial relationships with lipoproteins and apolipoproteins as in western populations. The relations of palmitic acid to serum lipids may be explained in terms of endogenous fat synthesis at a low-fat intake, rather than reflecting its relative intake.

  4. Modified lipoprotein-derived lipid particles accumulate in human stenotic aortic valves.

    Science.gov (United States)

    Lehti, Satu; Käkelä, Reijo; Hörkkö, Sohvi; Kummu, Outi; Helske-Suihko, Satu; Kupari, Markku; Werkkala, Kalervo; Kovanen, Petri T; Oörni, Katariina

    2013-01-01

    In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine -ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis.

  5. Secretion of hepatitis C virus envelope glycoproteins depends on assembly of apolipoprotein B positive lipoproteins.

    Directory of Open Access Journals (Sweden)

    Vinca Icard

    Full Text Available The density of circulating hepatitis C virus (HCV particles in the blood of chronically infected patients is very heterogeneous. The very low density of some particles has been attributed to an association of the virus with apolipoprotein B (apoB positive and triglyceride rich lipoproteins (TRL likely resulting in hybrid lipoproteins known as lipo-viro-particles (LVP containing the viral envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity of these particles has been shown to be higher than the infectivity of particles of higher density. The nature of the association of HCV particles with lipoproteins remains elusive and the role of apolipoproteins in the synthesis and assembly of the viral particles is unknown. The human intestinal Caco-2 cell line differentiates in vitro into polarized and apoB secreting cells during asymmetric culture on porous filters. By using this cell culture system, cells stably expressing E1 and E2 secreted the glycoproteins into the basal culture medium after one week of differentiation concomitantly with TRL secretion. Secreted glycoproteins were only detected in apoB containing density fractions. The E1-E2 and apoB containing particles were unique complexes bearing the envelope glycoproteins at their surface since apoB could be co-immunoprecipitated with E2-specific antibodies. Envelope protein secretion was reduced by inhibiting the lipidation of apoB with an inhibitor of the microsomal triglyceride transfer protein. HCV glycoproteins were similarly secreted in association with TRL from the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that proved deficient for lipoprotein assembly. These data indicate that HCV envelope glycoproteins have the intrinsic capacity to utilize apoB synthesis and lipoprotein assembly machinery even in the absence of the other HCV proteins. A model for LVP assembly is proposed.

  6. Aerobic exercise and lipids and lipoproteins in men: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kelley, George A; Kelley, Kristi S

    2006-01-01

    BACKGROUND: Aerobic exercise is recommended for improving lipoprotein and lipid levels which at less than their optimal levels are risk factors for cardiovascular disease. Evidence seems lacking for the effectiveness of exercise in reducing these levels, possibly due to small sizes in studies. We concluded a meta-analysis of the studies to examine the effects of aerobic exercise on lipids and lipoproteins in adult men. METHODS: Studies were retrieved via computerized literature searches, cross-referencing from retrieved articles, hand-searching, and expert review of our reference list. Inclusion criteria were randomized controlled trials, aerobic exercise ≥8 weeks, adult men ≥18 years of age, studies published in journal, dissertation, or master's thesis format, studies published in the English-language between January 1, 1955 and January 1, 2003, and assessment of one or more of the following lipids and lipoproteins: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDLC), and triglycerides (TG). All coding was conducted by both authors, independent of each other. Discrepancies were resolved by consensus. RESULTS: Forty-nine randomized controlled trials representing up to 67 outcomes from 2,990 men (1,741 exercise, 1,249 control) were pooled for analysis. Using random-effects modeling, statistically significant improvements were observed for TC, HDL-C and TG, and a trend for decreases was observed for LDL-C. Changes were equivalent to improvements of 2% for TC and HDL-C, 3% of LDL-C, and 9% for TG. CONCLUSIONS: Aerobic exercise reduces TC and TG and increases HDL-C in men 18 years of age and older.

  7. Surface display of a borrelial lipoprotein on meningococcal outer membrane vesicles.

    Science.gov (United States)

    Salverda, Merijn L M; Meinderts, Sanne M; Hamstra, Hendrik-Jan; Wagemakers, Alex; Hovius, Joppe W R; van der Ark, Arno; Stork, Michiel; van der Ley, Peter

    2016-02-17

    Outer Membrane Vesicles (OMVs) are gaining attention as vaccine candidates. The successful expression of heterologous antigens in OMVs, with the OMV functioning both as adjuvant and delivery vehicle, has greatly enhanced their vaccine potential. Since there are indications that surface exposed antigens might induce a superior immune response, targeting of heterologous antigens to the OMV surface is of special interest. Several systems for surface display of heterologous antigens on OMVs have been developed. However, these systems have not been used to display lipidated membrane-associated proteins known as lipoproteins, which are emerging as key targets for protective immunity. We were therefore interested to see whether we could express a foreign lipoprotein on the outer surface of OMVs. When outer surface protein A (OspA), a borrelial surface-exposed lipoprotein, was expressed in meningococci, it was found that although OspA was present in OMVs, it was no longer surface-exposed. Therefore, a set of fusions of OspA to different regions of factor H binding protein (fHbp), a meningococcal surface-exposed lipoprotein, were designed and tested for their surface-exposure. An N-terminal part of fHbp was found to be necessary for the successful surface display of OspA on meningococcal OMVs. When mice were immunized with this set of OMVs, an OspA-specific antibody response was only elicited by OMVs with clearly surface-exposed OspA, strengthening the idea that the exact positioning of an antigen in the OMV affects the immune response. This method for the surface display of heterologous lipoproteins on OMVs is a step forward in the development of OMVs as a vaccine platform.

  8. Mutants of Saccharomyces cerevisiae with defects in acetate metabolism: isolation and characterization of Acn- mutants.

    Science.gov (United States)

    McCammon, M T

    1996-09-01

    The two carbon compounds, ethanol and acetate, can be oxidatively metabolized as well as assimilated into carbohydrate in the yeast Saccharomyces cerevisiae. The distribution of acetate metabolic enzymes among several cellular compartments, mitochondria, peroxisomes, and cytoplasm makes it an intriguing system to study complex metabolic interactions. To investigate the complex process of carbon catabolism and assimilation, mutants unable to grow on acetate were isolated. One hundred five Acn- ("ACetate Nonutilizing") mutants were sorted into 21 complementation groups with an additional 20 single mutants. Five of the groups have defects in TCA cycle enzymes: MDH1, CIT1, ACO1, IDH1, and IDH2. A defect in RTG2, involved in the retrograde communication between the mitochondrion and the nucleus, was also identified. Four genes encode enzymes of the glyoxylate cycle and gluconeogenesis: ICL1, MLS1, MDH2, and PCK1. Five other genes appear to be defective in regulating metabolic activity since elevated levels of enzymes in several metabolic pathways, including the glyoxylate cycle, gluconeogenesis, and acetyl-CoA metabolism, were detected in these mutants: ACN8, ACN9, ACN17, ACN18, and ACN42. In summary, this analysis has identified at least 22 and as many as 41 different genes involved in acetate metabolism.

  9. Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

    Energy Technology Data Exchange (ETDEWEB)

    Cook, Melloni N. [University of Memphis; Dunning, Jonathan P [University of Memphis; Wiley, Ronald G [Vanderbilt University and Veterans Administration, Nashville, TN; Chesler, Elissa J [ORNL; Johnson, Dabney K [ORNL; Goldowitz, Daniel [University of Tennessee Health Science Center, Memphis

    2007-01-01

    We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsiveness to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.

  10. Mutants of downy mildew resistance in Lactuca sativa (lettuce).

    Science.gov (United States)

    Okubara, P A; Anderson, P A; Ochoa, O E; Michelmore, R W

    1994-07-01

    As part of our investigation of disease resistance in lettuce, we generated mutants that have lost resistance to Bremia lactucae, the casual fungus of downy mildew. Using a rapid and reliable screen, we identified 16 distinct mutants of Latuca sativa that have lost activity of one of four different downy mildew resistance genes (Dm). In all mutants, only a single Dm specificity was affected. Genetic analysis indicated that the lesions segregated as single, recessive mutations at the Dm loci. Dm3 was inactivated in nine of the mutants. One of five Dm 1 mutants was selected from a population of untreated seeds and therefore carried a spontaneous mutation. All other Dm1, Dm3, Dm5/8 and Dm7 mutants were derived from gamma- or fast neutron-irradiated seed. In two separate Dm 1 mutants and in each of the eight Dm3 mutants analyzed, at least one closely linked molecular marker was absent. Also, high molecular weight genomic DNA fragments that hybridized to a tightly linked molecular marker in wild type were either missing entirely or were truncated in two of the Dm3 mutants, providing additional evidence that deletions had occurred in these mutants. Absence of mutations at loci epistatic to the Dm genes suggested that such loci were either members of multigene families, were critical for plant survival, or encoded components of duplicated pathways for resistance; alternatively, the genes determining downy mildew resistance might be limited to the Dm loci.

  11. Forward genetic screen for auxin-deficient mutants by cytokinin.

    Science.gov (United States)

    Wu, Lei; Luo, Pan; Di, Dong-Wei; Wang, Li; Wang, Ming; Lu, Cheng-Kai; Wei, Shao-Dong; Zhang, Li; Zhang, Tian-Zi; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, Guang-Qin

    2015-07-06

    Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis.

  12. Dysfunctional lipoproteins from young smokers exacerbate cellular senescence and atherogenesis with smaller particle size and severe oxidation and glycation.

    Science.gov (United States)

    Park, Ki-Hoon; Shin, Dong-Gu; Cho, Kyung-Hyun

    2014-07-01

    Until now, there has been limited information on the effects of smoking on atherogenesis and senescence in the context of lipoprotein parameters, particularly in young smokers who have smoked fewer than 10 cigarettes per day for 3 years. In this study, lipoprotein profiles and functions were compared between smoker (n = 21) and control groups (n = 20). In the smoking group, ferric ion reduction abilities of serum and high-density lipoprotein (HDL) fractions were significantly reduced, and low-density lipoprotein (LDL) was severely oxidized. All lipoprotein particles from the smoker group showed higher advanced glycated end products with more triglyceride (TG) content compared with the control group. Lipoproteins from smokers showed faster agarose gel electromobility as well as greater smear band intensity in SDS-PAGE due to oxidation and glycation. LDL from smokers was more sensitive to oxidation and promoted foam cell forma-tion in macrophages. Gel filtration column chromatography revealed that the protein and cholesterol peaks of VLDL and LDL were elevated in the smoker group, whereas those of HDL were reduced. Human dermal fibroblast cells from the smoker group showed severe senescence following treatment with HDL2 and HDL3. Although HDL from young smokers showed impaired antioxidant ability, smaller particle size, and increased TG content, cholesteryl ester transfer protein activities were greatly enhanced in the serum and HDL fractions of the smoker group. In conclusion, smoking can cause production of dysfunctional lipoproteins having a smaller particle size that exacerbate senescence and atherogenic progress due to oxidation and glycation.

  13. Google: a narrativa de uma marca mutante

    Directory of Open Access Journals (Sweden)

    Elizete de Azevedo Kreutz

    2010-01-01

    Full Text Available As marcas mutantes já fazem parte de nossa realidade, embora ainda não totalmente percebidas e/ou aceitas como tal. O presente artigo busca refletir sobre a relevância dessas novas estratégias de comunicação e branding, identificando suas principais características. Para isso, utilizamos o método de estudo de caso, o Google, ancorado nos métodos de pesquisa bibliográfica e de internet. A escolha foi intencional, posto que a organização é referência em sua categoria, mecanismo de busca, e reflete essa estratégia comunicacional contemporânea. Como resultado, as informações obtidas nos possibilitam compreender essa tendência de comportamento de marca que busca a interação com seus públicos.

  14. Mutant p53: multiple mechanisms define biologic activity in cancer

    Directory of Open Access Journals (Sweden)

    Michael Paul Kim

    2015-11-01

    Full Text Available The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of p53 alterations involve missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may acquire novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in multiple model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 are reviewed and their limitations discussed.

  15. Colony mutants of compatible nocardiae displaying variations in recombining capacity.

    Science.gov (United States)

    Brownell, G H; Walsh, R S

    1972-03-01

    Colonial morphology mutants of Nocardia erythropolis were isolated following ultraviolet (UV) irradiation. The alleles rou-1/smo-1 were located by recombinant analysis and found to be linked to previously mapped characters. On the basis of recombinant class type patterns obtained from various selective characters it was postulated that the rou-1 allele may span a region of unique nucleotides in the Mat-Ce genome. Recombination frequencies of rou-1 and smo-2 bearing mutants of the Mat-Ce mating type were found to differ by over 1000 fold. Attempts to demonstrate that low recombination frequencies produced by the Smo mutants were due to Rec(-) genes were unsuccessful. No increased sensitivity to either UV or X irradiation was observed by the Smo mutants. Acriflavine treatment of either Rou or Smo colony mutants failed to accelerate reversion or to alter the recombining potentials of the mutants.

  16. Screening and identification of mutants of Magnaporthe grisea by REMI

    Institute of Scientific and Technical Information of China (English)

    XIONG Ruyi; LIU Juan; ZHOU Yijun; FAN Yongjian; ZHENG Xiaobo

    2007-01-01

    The plasmid pUCATPH was used to establish a transformation system in wild-type isolate M131 of Magnaporthe grisea.Six hundred and thirty-nine transformants were obtained by restriction enzyme-mediated integration (REMI) with hygromycin B (hyg B) resistance as a tag.Morphological analysis of two of the REMI mutants confirmed that they produced little melanin under black light and continued for three generations.Pathogenicity identification of six mutants screened proved that they made pathogenicity changes on three sets of differential varieties with different resistance genes.Rep-PCR analyses showed that two morphological mutants and two pathogenicity mutants differed from wild-type isolate M131 at the molecular level.RFLP analyses were performed to study the four mutants at the molecular level and the integration sites of the plasmid DNA.The results showed that the plasmid was inserted into all four mutants and that the insertion sites were random.

  17. Mutants of Cercospora kikuchii altered in cercosporin synthesis and pathogenicity

    Energy Technology Data Exchange (ETDEWEB)

    Upchurch, R.G.; Walker, D.C.; Rollins, J.A.; Ehrenshaft, M.; Daub, M.E. (North Carolina State Univ., Raleigh (United States))

    1991-10-01

    The authors have obtained spontaneous and UV-induced stable mutants, altered in the synthesis of cercosporin, of the fungal soybean pathogen Cercospora kikuchii. The mutants were isolated on the basis of colony color on minimal medium. The UV-induced mutants accumulated, at most, 2% of wild-type cercosporin levels on all media tested. In contrast, cercosporin accumulation by the spontaneous mutants was strongly medium regulated, occurring only on potato dextrose medium but at concentrations comparable to those produced by the wild-type strain. UV-induced mutants unable to synthesize cercosporin on any medium were unable to incite lesions when inoculated onto the soybean host. Cercosporin was reproducibly isolated from all inoculated leaves showing lesions. Although cercosporin involvement in disease has been indirectly suggested by many previous studies, this is the first report in which mutants blocked in cercosporin synthesis have been used to demonstrate that cercosporin is a crucial pathogenicity factor for this fungal genus.

  18. Mutants of Cercospora kikuchii Altered in Cercosporin Synthesis and Pathogenicity.

    Science.gov (United States)

    Upchurch, R G; Walker, D C; Rollins, J A; Ehrenshaft, M; Daub, M E

    1991-10-01

    We have obtained spontaneous and UV-induced stable mutants, altered in the synthesis of cercosporin, of the fungal soybean pathogen Cercospora kikuchii. The mutants were isolated on the basis of colony color on minimal medium. The UV-induced mutants accumulated, at most, 2% of wild-type cercosporin levels on all media tested. In contrast, cercosporin accumulation by the spontaneous mutants was strongly medium regulated, occurring only on potato dextrose medium but at concentrations comparable to those produced by the wild-type strain. UV-induced mutants unable to synthesize cercosporin on any medium were unable to incite lesions when inoculated onto the soybean host. Cercosporin was reproducibly isolated from all inoculated leaves showing lesions. Although cercosporin involvement in disease has been indirectly suggested by many previous studies, this is the first report in which mutants blocked in cercosporin synthesis have been used to demonstrate that cercosporin is a crucial pathogenicity factor for this fungal genus.

  19. Common Low-Density Lipoprotein Receptor p.G116S Variant Has a Large Effect on Plasma Low-Density Lipoprotein Cholesterol in Circumpolar Inuit Populations

    DEFF Research Database (Denmark)

    Dube, J. B.; Wang, J.; Cao, H.;

    2015-01-01

    BACKGROUND: Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p......10(-49)), which was >3x larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34-3.90; P=1.7x10(-17)), but did not have classical familial hypercholesterolemia...

  20. [Eremothecium ashbyii mutants resistant to 2,6-diaminopurine].

    Science.gov (United States)

    Stepanov, A I; Beburov, M Iu; Zhdanov, V G

    1975-01-01

    3 groups of Eremothecium ashbyii mutants resistant to 5-10(-3) M 2,6-diaminopurine (DAP) ahve been obtained. The mutants of the 1st group (Dap-r) are selected from the initial susceptible strain by the ability to grow in the presence of 5-10(-3) M DAP. The mutants of the 2nd group (Azg-Dap-r) are selected in the selective background of two analogues of 5-10(-3) M DAP and 10(-4) M 8-azaguanine (AG). The mutants of the 3rd group (Azg-r - DAP-r) are isolated from the mutant Azg-r 34 resistant to 10(-4) M AG. The results of studying cross-resistance of mutants to DAP, AG and 8-azaadenine (AA) show that Dap-r and Azg-Dap-r mutants in contrast to Azg-r - Dap-r, have common phenotypic properties and can grow only on the analogues of adenine. DAP, but not AA, eliminates the inhibitory effect of AG on the growth of these mutants. This effect is probably due to deaminating DAP to guanine. Mutants Azg-r - Dap-r retain the initial resistance to 10(-4) M AG, but are susceptible to higher concentrations of AG and in this case DAP does not eliminate the inhibitory effect of AG. In all mutants obtained the effectiveness of the incorporation of 14C-adenine (but not 14C-guanine) is sharply reduced, thus indicating the absence of adenosine-monophosphate pyrophosphorylase activity. The mutants do not excrete purine-like compounds into the medium. In the course of the continuous growth of mutants in the presence of DAP but not of guanine the red intracellular pigment is formed which seems to be a complex of riboflavin with DAP. A disturbance in the synthesis of adenosine monophosphate pyrophosphorylase does not influence practically the level of the synthesis of riboflavin in E. ashbyii.

  1. Preliminary study on a gravity-insensitive rice mutant

    Institute of Scientific and Technical Information of China (English)

    金静; 朱诚; 张红心; 孙宗修

    2004-01-01

    A gravity-insensitive mutant was isolated from rice (Oryza sativa L. Cv. Zhonghua 11) transformed by Agrobacterium tumefaciens. The mutant's shoot growth (prostrate growth) was insensitive to gravity; whereas root growth displayed a normal positive gravitropism.Histological observation of root caps and leaf sheaths indicated that there was no significant difference in the number and size of amyloplasts in cells of the mutant and cells of the wild type

  2. Preliminary study on a gravity-insensitive rice mutant

    Institute of Scientific and Technical Information of China (English)

    金静; 朱诚; 张红心; 孙宗修

    2004-01-01

    A gravity-insensitive mutant was isolated from rice (Oryza sativa L. cv. Zhonghua 11) transformed by Agrobacterium tumefaciens. The mutant's shoot growth (prostrate growth) was insensitive to gravity; whereas root growth displayed a normal positive gravitropism. Histological observation of root caps and leaf sheaths indicated that there was no significant difference in the number and size of amyloplasts in cells of the mutant and cells of the wild type.

  3. Fatty acid biosynthesis in novel ufa mutants of Neurospora crassa.

    Science.gov (United States)

    Goodrich-Tanrikulu, M; Stafford, A E; Lin, J T; Makapugay, M I; Fuller, G; McKeon, T A

    1994-10-01

    New mutants of Neurospora crassa having the ufa phenotype have been isolated. Two of these mutants, like previously identified ufa mutants, require an unsaturated fatty acid for growth and are almost completely blocked in the de novo synthesis of unsaturated fatty acids. The new mutations map to a different chromosomal location than previously characterized ufa mutations. This implies that at least one additional genetic locus controls the synthesis of unsaturated fatty acids in Neurospora.

  4. Polarized secretion of newly synthesized lipoproteins by the Caco-2 human intestinal cell line.

    Science.gov (United States)

    Traber, M G; Kayden, H J; Rindler, M J

    1987-11-01

    Lipoprotein secretion by Caco-2 cells, a human intestinal cell line, was studied in cells grown on inserts containing a Millipore filter (0.45 micron), separating secretory products from the apical and basolateral membranes into separate chambers. Under these conditions, as observed by electron microscopy, the cells formed a monolayer of columnar epithelial cells with microvilli on the apical surface and tight junctions between cells. The electrical resistances of the cell monolayers were 250-500 ohms/cm2. Both 14C-labeled lipids and 35S-labeled proteins were used to assess lipoprotein secretion. After a 24-hr incubation with [14C]oleic acid, 60-80% of the secreted triglyceride (TG) was in the basolateral chamber; 40% of the TG was present in the d less than 1.006 g/ml (chylomicron + VLDL) fraction and 50% in the 1.006 less than d less than 1.063 g/ml (LDL) fraction. After a 4-hr incubation with [35S]methionine, apolipoproteins were found to be major secretory products with 75-100% secreted to the basolateral chamber. Apolipoproteins B-100, B-48, E, A-I, A-IV, and C-III were identified by immunoprecipitation. The d less than 1.006 g/ml fraction was found to contain all of the major apolipoproteins, while the LDL fraction contained primarily apoB-100 and apoE; the HDL (1.063 less than d less than 1.21 g/ml) fraction principally contained apoA-I and apoA-IV. Mn-heparin precipitated all of the [35S]methionine-labeled apoB-100 and B-48 and a majority of the other apolipoproteins, and 80% of the [14C]oleic acid-labeled triglyceride, but only 15% of the phospholipid, demonstrating that Caco-2 cells secrete triglyceride-rich lipoproteins containing apoB. Secretion of lipoproteins was dependent on the lipid content of the medium; prior incubation with lipoprotein-depleted serum specifically reduced the secretion of lipoproteins, while addition of both LDL and oleic acid to the medium maintained the level of apoB-100, B-48, and A-IV secretion to that observed in the control

  5. Blood Lipoproteins under the Action of Exogenous Sex Steroids in the Postresuscitation Period

    Directory of Open Access Journals (Sweden)

    L. N. Shcherbakova

    2011-01-01

    Full Text Available Objective: to study the effect of reproductive hormones on the blood lipoprotein spectrum in the postresuscitation period after cardiac arrest. Materials and methods. Experiments were carried out on 66 mature albino rats of either sex weighing 200—250 g. Ten-minute cardiac arrest was induced by intrathoracic ligation of the vascular bundle. At 30 min after resuscitation, 49 animals were intramuscularly injected placebo and 17 animals were administered gyn-odian depot (Schering, Germany. The investigators measured the plasma concentrations of progesterone, 17-OH progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone, estradiol, and estriol, as well as the levels of triglycerides, total, and high-density lipoprotein (HDL, low-density lipoprotein (LDL, and very low-density lipoprotein (VLDL cholesterols. Blood was sampled on days 2 and 16 in the absence of therapy and on day 16 of sex steroid therapy. Results. By day 2 postresuscitation, the progesterone/estradiol ratio increased by approximately 1.8 times in males and females. Despite the fact that there were no changes in the concentrations of triglycerides, VLDL and HDL cholesterols in both males and females at that time, but the level of LDL cholesterol increased. Gender-related differences in the LDL spectrum by day 2 postresuscitation remained only in the levels of LDL cholesterol. Despite the normalization of progesterone levels, the concentrations of triglycerides and VLDL cholesterol decreased by day 16 of the postresuscitative period in the absence of therapy. There were no gender-related differences in the lipoprotein spectrum at this stage. The exogenous estradiol in combination with dehydroepiandrosterone caused a significant increase in the concentration of HLD cholesterol and a reduction in that of VLDL cholesterol in males and females both. Conclusion. Under gynodian action, the lipid spectrum was indicative of the exogenous estra-diol and

  6. Induced mutants from dihaploid potatoes after pollen mother cell treatment.

    Science.gov (United States)

    Przewoźny, T; Schieder, O; Wenzel, G

    1980-05-01

    Microspore mother cells of dihaploid Solanum tuberosum plants were mutagenically treated during the stage of meiosis. Mutagenesis was performed either by irradiation with x- or γ-rays or by the application of nitrosomethylurethane or methylnitronitrosoguanidine. Then, by use of the anther culture technique, 913 functional plants and 442 untreated control plants were regenerated. From the exposed plants seven distinct mutants could be isolated, predominantly chlorophyll deficient lines, while from the controls no clear-cut mutants arose. One mutant turned out to be photomorphogenetic in addition to having a chlorophyll defect. In addition to the production of mutants the treatments significantly increased the frequency of multicellular structure formation from microspores.

  7. plenty, a novel hypernodulation mutant in Lotus japonicus.

    Science.gov (United States)

    Yoshida, Chie; Funayama-Noguchi, Sachiko; Kawaguchi, Masayoshi

    2010-09-01

    Nitrogen fixation in nodules that contain symbiotic rhizobial bacteria enables legumes to thrive in nitrogen-poor soils. However, this symbiosis is energy consuming. Therefore, legumes strictly control nodulation at both local and systemic levels. Mutants deficient in such controls exhibit a range of phenotypes from non-nodulation to hypernodulation. Here, we isolated a novel hypernodulation mutant from the M(2) progeny derived from Lotus japonicus MG-20 seeds mutagenized by irradiation with a carbon ion beam. We named the mutant 'plenty' because it formed more nodules than the wild-type MG-20. The nodulation zone in the plenty mutant was wider than that in the wild type, but not as enhanced as those in other previously reported hypernodulation mutants such as har1, klv or tml of L. japonicus. Unlike these hypernodulation mutants, the plenty mutant developed nodules of the same size as MG-20. Overall, the plenty mutant exhibited a unique phenotype of moderate hypernodulation. However, a biomass assay indicated that this unique pattern of hypernodulation was a hindrance to host plant growth. The plenty mutant displayed some tolerance to external nitrates and a normal triple response to ethylene. Grafting experiments demonstrated that the root of plenty was responsible for its hypernodulation phenotype. Genetic mapping indicated that the PLENTY gene was located on chromosome 2.

  8. Characterization of host-range mutants of cyanophage N-1.

    Science.gov (United States)

    Sarma, T A; Kaur, B

    1997-10-01

    Fifteen host-range (h) mutants of cyanophage N-1 were characterized with reference to their efficiency of plating, time of appearance, morphology and size of plaques on Nostoc muscorum and its three phage-resistant (Nm 1/N-1, Nm 2/N-1 and Nm 8/N-1) mutants. While phage N-1 did not adsorb to the three phage-resistant mutants, the h mutants differed one from the other in having lower or higher adsorption rate constants on N. muscorum or the phage-resistant mutants. The inability of majority of h mutants isolated on Nm 1/N-1 to grow in Nm 8/N-1 was shown to be due to a failure of adsorption. The h mutants also differed one from the other in their reversion (back mutation) frequencies. The lethal doses (LD37) required to kill 37% of free phage particles after UV-irradiation, heating and ethylenediamine tetraacetate (EDTA) treatment greatly varied. Most of the h mutants were found to be considerably more sensitive to UV and thermic inactivation than N-1 while they were resistant to EDTA. The h mutants except five of them were unable to multiply at 40 degrees C. The significance of these features is discussed.

  9. Nigerian propolis improves blood glucose, glycated hemoglobin A1c, very low-density lipoprotein, and high-density lipoprotein levels in rat models of diabetes

    Science.gov (United States)

    Oladayo, Mustafa Ibrahim

    2016-01-01

    Objective: According to our previous studies, propolis of Nigerian origin showed some evidence of hypoglycemic and hypolipidemic activities in addition to its ability to ameliorate oxidative-stress-induced organ dysfunction. This study was carried out to determine whether an ethanolic extract of Nigerian propolis (EENP) improves glycated hemoglobin A1c (HbA1c), fasting plasma glucose, very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations in rats that have alloxan diabetes. Materials and Methods: Diabetes was induced with alloxan (110 mg/kg). Animals were divided into 5 groups (n = 5); Group 1 was non-diabetic receiving normal saline and Group 2 was diabetic but also received only normal saline. Groups 3, 4, and 5 were diabetic receiving 200 mg/kg propolis, 300 mg/kg propolis, and 150 mg/kg metformin, respectively, for 42 days. Results: Hyperglycemia, elevated serum level of VLDL, elevated plasma level of HbA1c, and decreased levels of HDL were observed in the diabetic untreated animals. Nigerian propolis decreased blood glucose level and serum level of VLDL but elevated HDL level. These changes were significant (P < 0.05). The levels of plasma HbA1c were also reduced in the propolis-treated groups, and the reduction was significant (P < 0.05). Conclusion: Nigerian propolis contains compounds exhibiting hypoglycemic, antihyperlipidemic, and HbA1c reducing activities. PMID:27366348

  10. A green tea catechin extract upregulates the hepatic low-density lipoprotein receptor in rats.

    Science.gov (United States)

    Bursill, Christina A; Roach, Paul D

    2007-07-01

    Green tea extracts have hypocholesterolaemic properties in epidemiological and animal intervention studies. Upregulation of the low-density lipoprotein (LDL) receptor may be one mechanism to explain this as it is the main way cholesterol is removed from the circulation. This study aimed to determine if a green tea extract could upregulate the hepatic LDL receptor in vivo in the rat. A green tea extract (GTE) enriched in its anti-oxidant constituents, the catechins, was fed to rats (n = 6) at concentrations of either 0, 0.5, 1.0 or 2.0% (w/w) mixed in with their normal chow along with 0.25% (w/w) cholesterol for 12 days. Administration of the GTE had no effect on plasma total or LDL cholesterol concentrations but high-density lipoprotein significantly increased (41%; p extract was able to increase the efflux of cholesterol from liver cells.

  11. Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein

    Institute of Scientific and Technical Information of China (English)

    Koichi; Sato; Fumikazu; Okajima

    2010-01-01

    The reverse cholesterol transport mediated by highdensity lipoprotein(HDL)is an important mechanism for maintaining body cholesterol,and hence,the crucial anti-atherogenic action of the lipoprotein.Recent studies,however,have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism.The present review provides an overview of the roles of sphingosine 1-phosphate(S1P)/S1P receptor and apolipoprotein A-I/ scavenger receptor class B typeⅠsystems in the antiatherogenic HDL actions.In addition,the physiological significance of the existence of S1P in the HDL particles is discussed.

  12. Effect of Sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Tremblay, AJ; Lamarche, B; Deacon, Carolyn F.;

    2011-01-01

    Aim: Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic triglyceride (TG)-rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase-4 that has been shown...... to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone-mediated improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid and incretin hormone levels as well...... as glucose homeostasis in patients with type 2 diabetes. Methods: Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m2) were recruited in this double-blind cross-over study using sitagliptin 100 mg/day or placebo...

  13. Poly-(R)-3-hydroxybutyrates (PHB) are Atherogenic Components of Lipoprotein Lp(a).

    Science.gov (United States)

    Reusch, Rosetta N

    2015-12-01

    The hypothesis is that poly-(R)-3-hydroxybutyrates (PHB), linear polymers of the ketone body, R-3-hydroxybutyrate (R-3HB), are atherogenic components of lipoprotein Lp(a). PHB are universal constituents of biological cells and are thus components of all foods. Medium chain-length PHB (70%) are absorbed by albumin, which transports them to the liver for disposal. When the amount of PHB in the diet exceed the capacity of albumin to safely remove them from the circulation, the excess PHB remain in the lipid core of LDL particles that become constituents of lipoprotein Lp(a), and contribute to the formation of arterial deposits. In summary, the presence of PHB – water-insoluble, dense, viscous, adhesive polymers – in the lipid cores of the LDL moieties of Lp(a) particles supports the hypothesis that PHB are atherogenic components of Lp(a).

  14. The low-density lipoprotein receptor gene family: a cellular Swiss army knife?

    Science.gov (United States)

    Nykjaer, Anders; Willnow, Thomas E

    2002-06-01

    The low-density lipoprotein receptor gene family is an evolutionarily conserved group of cell-surface receptors produced by mammals and other organisms. Initially thought to be endocytic receptors that mediate the uptake of lipoproteins, recent findings have shown that these receptors have other roles in a range of cellular processes. Among other activities, members of this family act as signal transducers in neuronal migration processes, regulate synaptic plasticity or control vitamin homeostasis. Such multifunctionality is achieved by interaction with diverse cell-surface proteins including glycolipid-anchored receptors, G-protein-coupled receptors and ion channels. Here, we review the molecular interactions of this protein family with other cell-surface proteins that provide specificity and versatility - a versatility that may be reminiscent of a cellular Swiss army knife.

  15. Immunohistochemical detection of a very high density lipoprotein (VHDL) in ovarian follicles of Triatoma infestans.

    Science.gov (United States)

    González, M S; Ronderos, J R; Rimoldi, O J; Brenner, R R

    2001-04-01

    The ability of Triatoma infestans ovarian follicles to synthesize a very high-density lipoprotein (VHDL) has been examined by immunohistochemical methods. This kind of lipoprotein can be envisaged as a storage hexameric protein present in the hemolymph of some insect species. VHDL immunoreactivity is observed in oocytes at different stages of maturation. The antigen is present in the oocyte cytoplasm as well as in the follicular epithelial cells. The immunopositive reaction in the apical surface of follicle cells suggests both a VHDL synthesis and a secretion process. Furthermore, VHDL seems to be stored into oocyte in yolk granules. On the contrary, no immunopositive reaction is observed in the intracellular spaces between follicle cells, suggesting that VHDL is not incorporated from hemolymph into the oocyte.

  16. High density lipoproteins as indicators of endothelial dysfunction in children with diadetes type I

    Directory of Open Access Journals (Sweden)

    Lobanova S.M.

    2011-12-01

    Full Text Available The aim of the investigation was to study the level of blood high density lipoproteins (HDL in the groups of children with different course of diadetes type I in order to find out the dependence of course and complications of diabetes on that level. Materials and methods: Blood high density lipoprotein (HDL levels were investigated in children and adolescents with diadetes type I, depending on the duration of diadetes type I, age, stage of sexual development, the stage of diabetic nephropathy and levels of plasma endothelin-1 (E-1. Results: Decrease in HDL level with increasing duration of diadetes type I in prepubertate patients, higher indices of HDL cholesterol were determined in girls, especially with impaired puberty. HDL cholesterol was higher in diabetic nephropathy at the stage of proteinuria and high level of blood endothelin-1. Conclusion: The revealed changes were considered to cause deregulation of vascular endothelium as a manifestation of the initial stages of endothelial dysfunction

  17. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Tybjaerg-Hansen, Anne; Steffensen, Rolf;

    2009-01-01

    CONTEXT: High levels of lipoprotein(a) are associated with increased risk of myocardial infarction (MI). OBJECTIVE: To assess whether genetic data are consistent with this association being causal. DESIGN, SETTING, AND PARTICIPANTS: Three studies of white individuals from Copenhagen, Denmark, were.......1-1.5), 1.1 (95% CI, 0.9-1.3), and 0.9 (95% CI, 0.8-1.1) in the CGPS (trend P = .005), and 1.4 (95% CI, 1.1-1.7), 1.2 (95% CI, 1.0-1.6), and 1.3 (95% CI, 1.0-1.6) in the CIHDS (trend P = .01). Genetically elevated lipoprotein(a) was associated with an HR of 1.22 (95% CI, 1.09-1.37) per doubling...

  18. [Influence of rapeseed oil on lipoprotein lipase activity in pigs (author's transl)].

    Science.gov (United States)

    Simonetti, M S

    1976-01-01

    Toxic activities in various animal species have shown for rapeseed oil. In this paper the influence of this oil on lipoprotein lipase activity of heart, liver and lung of pigs has been examined. The animals were fed with rapeseed oil with 40% erucic acid for 7, 15, 20 and 40 days. The control animals received olive oil. The results have shown a slight increase in the lipoprotein lipase activity in the heart of the pig after 20 days with rapeseed oil. In the liver this increase is particularly large in the pigs having been fed for 15 days both with rapeseed oil and olive oil. No differences were observed in the lung in the test and control animals with the only exception of animals fed for 20 days.

  19. Elevated plasma YKL-40, lipids and lipoproteins, and ischemic vascular disease in the general population

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Johansen, Julia S; Bojesen, Stig E;

    2015-01-01

    BACKGROUND AND PURPOSE: We tested the hypothesis that observationally and genetically elevated YKL-40 is associated with elevated lipids and lipoproteins and with increased risk of ischemic vascular disease. METHODS: We conducted cohort and Mendelian randomization studies in 96 110 individuals from......) or tripling (GG) in YKL-40 levels, but not with triglyceride levels or with risk of ischemic vascular disease. A doubling in YKL-40 was associated with a multifactorially adjusted observational hazard ratio for ischemic stroke of 1.18 (1.11-1.27), and a genetic odds ratio of 1.04 (0.95-1.15). Corresponding...... the Danish general population, with measured plasma levels of YKL-40 (n=21 647), plasma lipids and lipoproteins (n=94 461), and CHI3L1 rs4950928 genotype (n=94 579). RESULTS: From 1977 to 2013, 3256 individuals developed ischemic stroke, 5629 ischemic cerebrovascular disease, 4183 myocardial infarction...

  20. Causes and consequences of lipoprotein(a) abnormalities in kidney disease.

    Science.gov (United States)

    Kronenberg, Florian

    2014-04-01

    Lipoprotein(a) is one of the strongest genetically determined risk factors for cardiovascular disease, and patients with chronic kidney disease have major disturbances in lipoprotein(a) metabolism. Concentrations are increased and are influenced by glomerular filtration rate (GFR) and the amount of proteinuria. The reason for this elevation can be increased synthesis, as is the case for patients with nephrotic syndrome or those treated by peritoneal dialysis. In hemodialysis patients, a catabolic block is the reason for this elevation. The elevated concentrations might contribute to the tremendous cardiovascular risk in this particular population. In particular, the genetically determined small apolipoprotein(a) isoforms are associated with an increased risk for cardiovascular events and total mortality.